Advances in the study of exosomes in cardiovascular diseases

Zhaobo Zhang; Yuanming Zou; Chunyu Song; Kexin Cao; Kexin Cai; Shuxian Chen; Yanjiao Wu; Danxi Geng; Guozhe Sun; Naijin Zhang; Xingang Zhang; Yixiao Zhang; Yingxian Sun; Ying Zhang

doi:10.1016/j.jare.2023.12.014

. 2023 Dec 18;66:133–153. doi: 10.1016/j.jare.2023.12.014

Advances in the study of exosomes in cardiovascular diseases

Zhaobo Zhang ^a, Yuanming Zou ^a, Chunyu Song ^a, Kexin Cao ^a, Kexin Cai ^a, Shuxian Chen ^a, Yanjiao Wu ^a, Danxi Geng ^a, Guozhe Sun ^a,^⁎, Naijin Zhang ^a,^b,^c,^⁎, Xingang Zhang ^a,^⁎, Yixiao Zhang ^d,^⁎, Yingxian Sun ^a,^b,^⁎, Ying Zhang ^a,^b,^⁎

PMCID: PMC11674797 PMID: 38123019

Graphical abstract

Highlights

•
Exosomes are essential communication mediators in the cardiovascular system.
•
Exosomes miRNAs play an essential role in pathological processes such as inflammatory responses, angiogenesis, cell migration, and fibrosis.
•
Exosomes have great potential as diagnostic markers for cardiovascular diseases in clinical practice.

Abstract

Background

Cardiovascular disease (CVD) has been the leading cause of death worldwide for many years. In recent years, exosomes have gained extensive attention in the cardiovascular system due to their excellent biocompatibility. Studies have extensively researched miRNAs in exosomes and found that they play critical roles in various physiological and pathological processes in the cardiovascular system. These processes include promoting or inhibiting inflammatory responses, promoting angiogenesis, participating in cell proliferation and migration, and promoting pathological progression such as fibrosis.

Aim of review

This systematic review examines the role of exosomes in various cardiovascular diseases such as atherosclerosis, myocardial infarction, ischemia–reperfusion injury, heart failure and cardiomyopathy. It also presents the latest treatment and prevention methods utilizing exosomes. The study aims to provide new insights and approaches for preventing and treating cardiovascular diseases by exploring the relationship between exosomes and these conditions. Furthermore, the review emphasizes the potential clinical use of exosomes as biomarkers for diagnosing cardiovascular diseases.

Key scientific concepts of review

Exosomes are nanoscale vesicles surrounded by lipid bilayers that are secreted by most cells in the body. They are heterogeneous, varying in size and composition, with a diameter typically ranging from 40 to 160 nm. Exosomes serve as a means of information communication between cells, carrying various biologically active substances, including lipids, proteins, and small RNAs such as miRNAs and lncRNAs. As a result, they participate in both physiological and pathological processes within the body.

Introduction

Cell-to-cell communication occurs through direct contact, paracrine signaling, and extracellular vesicles (EVs) [1]. EVs are vital for normal tissue function and regulating disease progression [2]. Although the classification standards of EVs are constantly evolving, they are generally divided into two categories: ectosomes with a diameter of 50–1000 μm and exosomes with a relatively small diameter (usually 40–160 nm) [3]. Almost all cells are capable of releasing exosomes, which contain various types of biomacromolecules such as proteins and miRNAs and can regulate their targets accordingly [4]. Exosomes exhibit heterogeneity in their roles due to different recipient cells, and their effects vary depending on the type of exosome received by the same type of cell [5]. Their biocompatibility and ability to pass through the body's biofilm barrier make them ideal for long-distance transmission of physiological and pathological signals. As a result, exosomes have become a popular research direction in recent years and have been extensively studied in scientific research [6].

The above study indicates that exosomes can participate in intercellular communication and signal transduction through various mechanisms. This provides the potential for exosomes to play a regulatory role in various physiological and pathological processes. Increasing evidence shows a close association between extracellular vesicles released by various cells and the occurrence, development, and treatment of cardiovascular diseases [7], [8]. Cardiovascular disease is the leading cause of premature death for over 40 % of Chinese people, placing a significant burden on public health [9]. The heart is a complex muscular pump responsible for maintaining normal blood pressure and supplying nutrients and oxygen to the entire body through rhythmic contraction and relaxation. Various cardiac cell-derived exosomes, including cardiomyocytes, fibroblasts, cardiac progenitor cells, endothelial cells, and vascular smooth muscle cells, have been linked to the development of heart disease [7], [8]. This review aims to summarize the progress of exosomes in several cardiovascular diseases with high incidence and impact, highlighting the role of exosomes in the physiological and pathological processes of these diseases, as well as their potential use in treating cardiovascular diseases. Additionally, the potential clinical application of exosomes as biomarkers for diagnosing cardiovascular diseases is also discussed.

Biogenesis, composition, mechanisms, and functions of exosomes

1. Biogenesis process of exosomes

The generation of exosomes mainly involves five steps: endocytosis and inward budding of the plasma membrane, formation of early sorting endosomes (ESE), maturation of late sorting endosomes (LSE), formation of multivesicular bodies (MVB), and finally, the release of exosomes [3]. Firstly, the inward budding of the cell membrane through endocytosis allows the encapsulation of extracellular fluid components, as well as proteins, lipids, and small molecules, into the cell. During this process, the inward-budded membrane fuses with the endoplasmic reticulum, Golgi apparatus, and even mitochondria to form early sorting endosomes (ESE). ESE can mature into late sorting endosomes (LSE), where secondary inward budding results in the formation of intraluminal vesicles (ILV) containing cellular components such as proteins, nucleic acids, and lipids, ultimately leading to the formation of multivesicular bodies (MVB). Subsequently, MVB can interact with intracellular autophagosomes or lysosomes for degradation, or it can approach the cell membrane through the cellular cytoskeleton and microtubule system, ultimately releasing exosomes through exocytosis [10]. Proteins essential for the transport, including endosomal sorting complex required for transport (ESCRT) proteins, ALIX (apoptosis-linked gene 2-interacting protein X), tumor susceptibility gene 101 (TSG101), and Rab proteins (Rab27a/b), have been demonstrated to participate in the generation process of exosomes [11].

2. Mechanisms of action of exosomes

Existing research suggests that exosomes exert their effects mainly through three mechanisms [12]. Firstly, it has been confirmed by multiple studies that exosomes and target cells directly interact with each other through ligands and receptors on their respective membranes, such as proteins, sugars, and lipids [13], [14], [15]. Among these known direct interactions, protein–protein interactions account for the largest proportion. For example, dendritic cells can transfer membrane proteins such as major histocompatibility complex class II (MHC II) as exosomes to homologous T cells, playing an immune regulatory role. This process depends on the interaction between ICAM-1 on the surface of mature dendritic cell exosomes and CD28 on the surface of T cells [16], [17]. Similarly, it was found that the ability of tumor cells to uptake exosomes was significantly inhibited after treatment with proteinase K to remove surface proteins from exosomes [13]. Secondly, the indirect communication mediated by soluble ligands is that exosomes do not directly contact the target cells, but first break down into soluble proteins and then interact with cell surface receptors to activate various signal transduction pathways. For example, tumor cells shed membrane cofactor protein (MCP) from exosomes, which is then converted into an active form by metal protease after enzymatic hydrolysis [18]. Thirdly, the receptor cells take up exosomes by endocytosis. This endocytosis includes clathrin-dependent endocytosis, caveolae-dependent endocytosis, macropinocytosis, phagocytosis, and lipid raft-mediated endocytosis. Clathrin induces the cell membrane to invaginate, envelop the contents of the exosomes and pinch off inward, forming a larger vesicle [19]. Unlike clathrin-forming lipid valves, caveolae form a stable trimer complex with caveolin-1, -2, and -3 to mediate the internalization process [20]. Unlike the above two methods, macropinocytosis and phagocytosis can form larger vacuoles. Macropinocytosis absorbs extracellular fluid and substances by forming folds of the cell membrane, while phagocytosis depends on the binding of membrane receptors and ligands [21]. Lipid rafts are formed by microdomains rich in cholesterol and sphingolipids as well as protein receptors, and their endocytosis is related to their lipid microdomain components [21].

3. Biological functions of exosomes

It has been confirmed that exosomes participate in various physiological and pathological processes. Typically, exosomes can directly transfer their contents, such as proteins, nucleic acids, and lipids, to target cells, thereby regulating their biological functions, with nucleic acids playing a predominant role [22]. For instance, studies have found that exosomes derived from mesenchymal stem cells are rich in miR-125a-5p. When specifically administered to a pig model of ischemia–reperfusion injury, it significantly restrains adverse cardiac remodeling and improves cardiac function [23]. Furthermore, exosomes can also engage in intercellular communication directly through their surface proteins. In another study, it was observed that exosomes interact with other cells through their surface proteins, potentially modulating antigen presentation and immune regulation processes in the immune system [24]. Specific biological functions of exosomes in cardiovascular diseases will be detailed in the next section.

The relationship between exosomes and cardiovascular diseases

1. Atherosclerosis

1.1. Introduction to atherosclerosis

Atherosclerosis (AS) is a chronic inflammatory disease characterized by fibrofatty lesions in the arterial wall, where macrophages uptake modified lipoproteins and transform into foam cells, marking the initiation process [25]. Its development may be associated with the transport of low-density lipoprotein (LDL) [26], making it a significant cause of global mortality and a crucial factor in ischemic diseases such as coronary heart disease and myocardial infarction [27], [28]. Atherosclerosis involves a complex vascular remodeling process, encompassing various phenotypic changes related to the vasculature, including endothelial cell dysfunction, abnormal proliferation, and migration of vascular smooth muscle cells into the intima, as well as the infiltration and activation of inflammatory cells. Additionally, macrophages can polarize into pro-inflammatory phenotypes, releasing numerous inflammatory factors and proteases, thereby exacerbating the pathology [29], [30], [31]. These changes result from the interaction of multiple cell types and factors, highlighting the crucial role of cell communication mediated by exosomes in the occurrence and development of atherosclerosis [32], [33]. Exosomes can either promote or inhibit atherosclerosis, depending on the state of the cell of origin. When derived from inflammatory or pro-atherosclerotic cells, exosomes can carry corresponding molecules into target cells, altering their phenotype and driving disease progression. Conversely, exosomes from normal anti-inflammatory and anti-atherosclerotic cells contain protective molecules that can prevent lesion formation. In summary, exosomes exert bidirectional regulatory effects, serving as an extension of source cell functional states, mediating intercellular signaling, and participating in the development or inhibition of atherosclerosis [34].

1.2. Relationship between exosomes of different cellular origins and atherosclerosis Fig. 1

1.2.1. Circulating exosomes

Despite increasing evidence indicating the crucial role of exosomes in stabilizing atherosclerotic plaques, the role and mechanisms of circulating exosomes in the formation of atherosclerotic plaques remain to be further investigated [35], [36]. A recent study indicates an increased level of exosomes in the plasma of coronary heart disease patients, among which circular RNA circ_0001785 acts as a competitive endogenous RNA (ceRNA), “sponging” the expression of miR-513a-5p in endothelial cells. This leads to elevated downstream TGFBR3 protein expression, promoting endothelial cell proliferation and migration, and inhibiting endothelial cell apoptosis, thus delaying the onset of atherosclerosis [37].

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is present on the surfaces of various vascular cells, including endothelial cells, monocytes/macrophages, and vascular smooth muscle cells. Its mediation of oxLDL uptake leads to foam cell formation, promoting the development of atherosclerosis [38]. Conversely, in patients with acute myocardial infarction, the expression of miR-186-5p in serum exosomes is decreased compared to the healthy control group. This reduction leads to the relief of miR-186-5p's inhibitory effect on LOX-1, exacerbating lipid accumulation and worsening atherosclerosis. Conversely, a miR-186-5p mimic exhibits a protective effect against atherosclerosis [39].

1.2.2. Inflammatory cell-derived exosomes

1.2.2.1. Macrophage-derived exosomes

NF-κB, as a classical pro-inflammatory signaling pathway, is regulated by various positive and negative components that collectively control cell gene expression and various life activities [40]. Within the cytoplasm, the transcription factor RelA (P65) forms a heterodimer with the p50 protein, and this heterodimer binds to the inhibitory protein IκBα, maintaining an inhibited state. When extracellular signaling molecules such as TNF-α can activate IκB kinase (IKK), IκBα undergoes phosphorylation and dissociates from the heterodimer, ultimately being degraded through the proteasome pathway. The activated heterodimer then translocates to the cell nucleus, serving as a transcription factor to bind DNA and regulate gene expression [41], [42], [43]. The interaction between the transcription factor specificity protein 1 (SP1) and P65 in endothelial cells has been confirmed to play a crucial regulatory role in various pathological processes, including atherosclerosis [44], [45], [46]. Recent studies have indicated that exosomes derived from macrophages can be internalized by endothelial cells. They target and degrade SP1 mRNA, reducing SP1 expression. This activates the NF-κB signaling pathway, promotes the expression of vascular adhesion molecules, causes endothelial dysfunction, and participates in the process of atherosclerosis [47]. When the NF-κB signaling pathway is activated, macrophages polarize towards the M1 subtype, exerting pro-inflammatory effects and inducing the production of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α). Simultaneously, TNF-α can activate the NF-κB signaling pathway, creating a positive feedback loop that intensifies the inflammatory response [40].

SHIP2 is the gene encoding inositol phosphatase 2, expressed highly in VSMCs, and the encoded enzyme exhibits phosphatase activity within cells [48]. The PI3K/AKT/mTOR pathway is a classical signaling pathway in the development of atherosclerosis [49]. Platelet-derived growth factor (PDGF) and insulin-like growth factor I (IGF-I) have been demonstrated as growth factors with anti-apoptotic effects in the development of atherosclerosis. Both can promote PI3K activation, where phosphatidylinositol (PI) continuously combines with phosphate groups to eventually form PIP3, initiating the PI3K/AKT/mTOR signaling pathway. Interestingly, SHIP2 in VSMCs can deactivate the PI3K/AKT/mTOR signaling pathway by degrading PIP3, negatively regulating PDGF and IGF-I, thereby inhibiting the proliferation of VSMCs [50]. Recent studies have demonstrated that oxidized low-density lipoprotein (ox-LDL) can stimulate macrophages to produce exosomes enriched with miR-186–5p. When these exosomes are internalized by vascular smooth muscle cells, miR-186–5p deactivates SHIP2, thus rescuing the PI3K/AKT/mTOR pathway and promoting the proliferation and migration abilities of VSMCs and the development of atherosclerosis [51].

Smoking has been proven to be a significant cause of endothelial dysfunction and vascular calcification, closely associated with (sub)clinical atherosclerosis [52]. Nicotine, the primary harmful substance in tobacco, not only enhances pro-inflammatory communication between macrophages and vascular smooth muscle cells but also directly stimulates the migration of lipid plaques, accelerating the progression of atherosclerosis [53]. The loss or inhibition of PTEN has been confirmed to promote the proliferation and migration of vascular smooth muscle cells (VSMCs) [54], [55]. Relevant studies have shown that nicotine can stimulate macrophages to produce exosomes containing miR-21-3p. This miR-21-3p can inhibit PTEN, affecting the functionality of VSMCs, and thereby promoting the formation of lipid plaques and advancing atherosclerosis [56].

Furthermore, researchers have found that exosomes derived from interleukin-4 (IL-4)-stimulated bone marrow-derived macrophages (BMDM-IL-4-exo) contain microRNAs such as miR-99a-5p, miR-146b-5p, and miR-378-3p, which can selectively inhibit the TNF-α/NF-κB inflammatory signaling pathway, exerting anti-inflammatory effects and delaying the progression of atherosclerosis [57].

1.2.2.2. Other inflammatory cell-derived exosomes

Circular RNA, as a type of non-coding RNA, has been reported this year to be involved in the progression of coronary artery disease (CAD) [58], [59]. Research has found that exosomes derived from monocytes of CAD patients, containing CircNPHP4, act as competitive endogenous RNA (ceRNA), interacting with miR-1231. This interaction alleviates the endogenous expression inhibition of epidermal growth factor receptor (EGFR) by miR-1231, thereby promoting downstream PI3K/Akt signaling and the expression of intercellular adhesion molecules ICAM-1 and VCAM-1. Ultimately, it enhances heterotypic adhesion between monocytes and vascular endothelial cells [60]. Additionally, mature dendritic cells can participate in endothelial inflammation through exosomes mediated by the TNF-α/NF-κB pathway, exacerbating atherosclerosis [61]. Dendritic cells can also transfer exosomal miR-203-3p to bone marrow-derived macrophages, selectively inhibiting the expression of lysosomal protease—cathepsin S, which may lead to inflammatory diseases, thereby slowing down the progression of atherosclerosis [62].

1.2.3. Mesenchymal stem cell-derived exosomes

Exosomes derived from mesenchymal stem cells also play a crucial role in the development and treatment of atherosclerosis. For instance, exosomal miR-21a-5p and miR-let7 from mesenchymal stem cells can reduce macrophage infiltration, promote M2 reparative polarization, and alleviate atherosclerosis [63], [64]. Similarly, exosomes derived from adipose tissue-derived mesenchymal stem cells (ADSCs) containing miR-342-5p can protect endothelial cells from atherosclerotic damage [65]. Peroxisome proliferator-activated receptor gamma (PPARγ) enhances cholesterol efflux by inducing liver X receptor alpha (LXRα) and phospholipid transport ATPase (ABCA1) transcription. Specifically knocking out the lncRNA LOC100129516 in exosomes derived from mesenchymal stem cells can upregulate the PPARγ/LXRα/ABCA1 signaling pathway, improving atherosclerosis [66]. Similar to the NF-κB signaling pathway, Wnt/β-catenin is a classical pro-inflammatory signaling pathway, as reported in previous studies [67], [68]. FZD5 is an auxiliary receptor in the Wnt/β-catenin pathway, participating in its activation. Research indicates that exosomal miR-100-5p from human umbilical cord mesenchymal stem cells suppresses eosinophilic granulocyte inflammation through the FZD5/Wnt/β-catenin pathway, alleviating atherosclerosis [69].

1.2.4. Endothelium-derived exosomes

Neutrophils can be activated under specific stimuli to release neutrophil extracellular traps (NETs), which are typically defined as a mesh-like structure composed of chromatin, neutrophil-derived nuclei, and granule proteins, exhibiting cytotoxicity and promoting thrombosis. NETs play a crucial role in the plaque formation process of atherosclerosis (AS) [70]. Research suggests that oxidized low-density lipoprotein (ox-LDL) can activate the NF-κB signaling pathway in vascular endothelial cells (VECs), leading to the release of exosomal miR-505. This induction promotes the formation of neutrophil extracellular traps (NETs), exacerbating atherosclerosis [71]. Similarly, exosomes derived from ox-LDL-treated endothelial cells containing long non-coding RNA (lncRNA) MALAT1 can also induce the formation of neutrophil extracellular traps (NETs), further worsening the development of atherosclerosis [72]. Furthermore, ox-LDL can stimulate macrophages to release exosomal miR-146a. MiR-146a, by downregulating the expression of superoxide dismutase 2 (SOD2), leads to increased reactive oxygen species (ROS) and oxidative stress, promoting the formation of NETs [73].

Autophagy is a process mediated by lysosomes within cells, degrading damaged organelles and large molecular proteins after misfolding for subsequent reuse [74]. Moderate autophagy can reduce foam cell formation, stabilize lipid plaques, and slow the progression of atherosclerosis. However, excessive autophagy activation can lead to plaque instability and increased inflammation [75]. Endothelial colony-forming cells (ECFCs), a type of endothelial progenitor cells, release exosomal miR-21-5p, which inhibits the expression of autophagy-related protein SIPA1L2 in oxLDL-treated endothelial cells. This increases autophagic flux, promoting endothelial cell proliferation and migration, and mitigating vascular damage caused by atherosclerosis [76].

1.2.5. Adipocyte-derived exosomes

Obesity is one of the significant risk factors for the occurrence and development of atherosclerosis [77]. In recent years, Stephen and colleagues discovered that adipocytes can release fat-derived exosomes independently of the classical lipase hydrolysis pathway, supplying nearby macrophages and modulating their differentiation and functions [78]. Research indicates that visceral adipose tissue from different locations regulates macrophage transformation into foam cells and promotes M1 polarization, accelerating the development of atherosclerosis through its derived exosomes [79]. For instance, exosome-derived miR-34a from adipocytes, when transported into adjacent macrophages, targets and downregulates the transcription factor KLF4, promoting M1 polarization and exacerbating systemic inflammation and metabolic dysfunction caused by obesity [80]. Similarly, peroxisome proliferator-activated receptor (PPAR), a member of anti-inflammatory nuclear receptors, is targeted by exosome-derived miR-27b-3p from visceral adipocytes, activating the NF-κB pathway and promoting endothelial inflammation and atherosclerosis [81]. Adipocytes can also release exosomes containing long-chain non-coding RNA SNHG9. After uptake by vascular endothelial cells, these vesicles form an RNA-induced silencing complex with Ago2 protein, binding to TRADD mRNA and inhibiting TRADD expression, thereby alleviating inflammation and apoptosis in endothelial cells and exerting a protective effect [82]. Furthermore, studies have found that insulin-resistant adipocyte-derived exosomes in ApoE −/− diabetic mice can enhance vascularization, leading to the further promotion of vulnerable plaque and atherosclerosis development due to the loose structure of newly formed blood vessels [83].

1.2.6. Platelet-derived exosomes

Although the role of platelets in atherosclerosis has been well elucidated, the role of platelet-released exosomes (P-EXOs) in this process remains to be further investigated [84], [85]. Previous studies have confirmed that P-EXOs can inhibit platelet activation and thrombus formation, possibly by promoting protein ubiquitination and degradation of CD36 on macrophage surfaces, thereby inhibiting ox-LDL absorption and foam cell formation [86]. Subsequent studies have found that miRNA-223 in P-EXOs can block the classical inflammatory signaling pathways NF-κB and MAPK by inhibiting phosphorylation of p38, JNK, and ERK, thereby suppressing the expression of ICAM-1 and attenuating the inflammatory response in endothelial cells [87]. Similarly, in line with the above research results, Ye Yao and colleagues found that P-EXOs with high expression of miR-25-3p can target and inhibit the NF-κB signaling pathway in endothelial cells. The expression of A disintegrin and metalloproteinase domain 10 (ADAM10) gene is suppressed, ultimately leading to downregulation of the inflammatory factors IL-1β, IL-6, and TNF-α [88].

1.3. Therapeutic and clinical perspectives related to exosomes in atherosclerosis

As the pathological process of atherosclerosis continues to progress, vascular stent implantation surgery has become an effective treatment for late-stage atherosclerotic vascular occlusion. However, the occurrence of in-stent restenosis (ISR) limits the long-term efficacy of the stent [89]. Defects in efferocytosis lead to the inability of apoptotic cells beneath the implanted stent to be promptly cleared, triggering an inflammatory response. To prevent this process, researchers have recently developed a vascular stent loaded with pro-efferocytotic exosomes. This stent releases exosomes in the presence of Lipoprotein-associated phospholipase A2 (Lp-PLA2), enhancing the clearance of apoptotic cells and reducing the thickness of the vascular intima [90]. It is well known that Smad3 is crucial for regulating the differentiation/contractile phenotype of vascular smooth muscle cells (VSMCs), and the loss of Smad3 leads to increased proliferation of VSMCs [91]. Studies have shown that endothelial cell-derived exosomal miR-501-5p can target Smad3, promoting the proliferation and migration of VSMCs, and leading to in-stent restenosis [92]. Additionally, research has reported that exosomes derived from M2-type macrophages can upregulate Activator Protein-1 (AP-1), a transcription factor involved in the proliferation and migration of VSMCs, promoting the dedifferentiation of VSMCs. This provides a novel solution for promoting vascular tissue repair and reducing the formation of ISR after stent implantation [93].

2. Myocardial infarction

2.1. Introduction to myocardial infarction

The clinical definition of myocardial infarction (MI) was proposed by the American Journal of Cardiology in 2018, indicating the presence of acute myocardial injury detected through abnormal cardiac biomarkers in the presence of evidence of acute myocardial ischemia [94]. Even with the current advanced level of medical care, myocardial infarction (MI), despite being maximally protected through timely thrombolysis or percutaneous coronary intervention (PTCI) methods, remains a cardiovascular disease associated with high mortality worldwide [95].

2.2. Relationship between exosomes of different cellular origins and myocardial infarction Fig. 2

2.2.1. Circulating exosomes

There is already evidence indicating that exosomes from the plasma of healthy individuals can exert protective effects on the heart under ischemic conditions [96]. Bo Wang and colleagues' study confirmed that the compromised protective function of the myocardium in the acute phase of myocardial infarction is associated with the downregulation of exosomal miR-342-3p in circulation. Under normal circumstances, miR-342-3p targets TFEB and SOX6 genes, inhibiting the autophagy and apoptosis processes of myocardial cells [97].

Recent studies suggest that exosomes from the plasma of newborn mice may potentially improve myocardial infarction by modulating vascularization in cardiac endothelial cells. Targeted promotion of vascularization, considered a key factor in improving cardiac prognosis after myocardial infarction, can reduce infarct size and cell death. Previous research has confirmed nitric oxide (NO) as a protective molecule in endothelial cells, promoting proliferation, migration, and reducing apoptosis [98], [99]. A study proposed that myocardial ischemia patients exhibit low expression of miR-939-5p in coronary artery serum exosomes (isc-Exos), leading to weakened targeted inhibition on the 3′-UTR of inducible nitric oxide synthase (iNOS). This results in increased NO synthesis and enhanced vascularization response [100]. The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase regulating various cellular processes, and tuberous sclerosis complex 1 (TSC1), typically forming a complex with TSC2, co-negatively regulates mTOR complex 1 (mTORC1) [101]. Research has found that exosomes (AMI-Exos) from the peripheral blood of acute myocardial infarction (AMI) patients contain miR-126-3p targeting mTORC1. This leads to increased expression of hypoxia-inducible factor (HIF-1α), an essential mediator downstream of VEGF induction for vascularization, promoting angiogenesis [102], [103], [104]. Additionally, research has shown that exosomes (AMI-Exos) from the peripheral blood of acute myocardial infarction (AMI) patients carry miR-126-3p, targeting mTORC1 and increasing the expression of hypoxia-inducible factor (HIF-1α). This promotes angiogenesis by upregulating VEGF induction, a crucial mediator for vascularization [102], [103], [104]. Furthermore, the research team led by Huili Li discovered that the expression of miR-26b-5p in plasma exosomes from acute myocardial infarction (AMI) patients is downregulated. Targeted inhibition of downstream iron death markers suggests a weakened capacity of solute carrier family 7 member 11 (SLC7A11), thereby inhibiting iron death following myocardial infarction and providing a new therapeutic strategy for AMI [105].

2.2.2. Immune cell-derived exosomes

When myocardial infarction (MI) occurs, a large number of myocardial cells die within a few hours, accompanied by the release of numerous danger-associated molecular patterns (DAMPs), which are produced by host tissues or immune cells in response to stress or tissue damage [106]. DAMPs associated with MI mainly include heat shock proteins and high mobility group box (HMGB)-1. They bind to pattern recognition receptors on neutrophils, macrophages, or within the cytoplasm, activating the early inflammatory response after MI to eliminate damaged or dead cells [107]. The inflammatory response involving various immune cells plays a crucial role in myocardial cell dysfunction, damage, necrosis, and ventricular remodeling after myocardial infarction (MI). Therefore, understanding the specific mechanisms of the inflammatory response after MI and choosing appropriate anti-inflammatory measures are essential for the prognosis after myocardial infarction [108].

Macrophages play a central role in the immune response after myocardial infarction (MI) and exhibit dual functions [109]. Previous studies have indicated that in the early stages of myocardial infarction (MI) (within the first 5 days), neutrophils and pro-inflammatory M1 macrophages play a predominant role, while during the repair phase (after 5 days), neutrophils rapidly die, inducing macrophage polarization toward the anti-inflammatory M2 subtype, contributing to the resolution of inflammation and tissue repair [110].

Recent research has found that M1 subtype macrophages can secrete exosomes containing miR-155, which, upon uptake by vascular endothelial cells, inhibit downstream targets, including SIRT1, AMPK, eNOS, RAC1, and PAK2 [111]. SIRT1 and AMPK mediate deacetylation and phosphorylation processes, respectively, both of which can activate eNOS. The Sirt1/AMPK-eNOS pathway is an important mechanism for maintaining endothelial cell homeostasis, while the RAC1–PAK1/2 pathway is primarily involved in mediating lumen formation and vascular homeostasis [112]. Furthermore, exosome miR-155 can also be taken up by fibroblasts, mediating inflammatory responses and inhibiting proliferation, thereby damaging myocardial cells [113]. Therefore, exosome miR-155 derived from M1 macrophages can selectively inhibit the above pathways, reduce endothelial cell migration, and suppress angiogenesis, exacerbating the myocardial injury and hindering its healing after myocardial infarction [111]. In contrast to the M1 subtype, exosome miR-1271-5p derived from M2 macrophages can alleviate myocardial apoptosis induced by acute myocardial infarction by selectively inhibiting the transcription factor SOX6, thereby promoting cardiac repair [114]. In line with these research findings, a study emphasizes that knocking down SOX6 can balance the expression of normal slow muscle fibers and skeletal fast muscle fibers in the heart, thereby maintaining normal cardiac function [115]. During the repair phase of myocardial infarction, M2 macrophages also secrete cytokines such as IL-10 and TGF-β to promote the myocardium's anti-inflammatory repair process.

In addition to macrophages, regulatory T cells (Tregs) [116], dendritic cells (DC) [117], [118], [119], and mast cell-derived exosomes [120] play important roles in the inflammatory response after myocardial infarction, and understanding these mechanisms provides targeted therapeutic targets for the treatment of myocardial infarction.

2.2.2. Mesenchymal stem cell-derived exosomes

Mesenchymal stem cells (MSCs) are a type of stromal cells with self-renewal and multipotent differentiation potential. They primarily exert therapeutic effects in cardiovascular diseases through paracrine mechanisms mediated by exosomes. These mechanisms involve reducing apoptosis, inhibiting ferroptosis, improving pyroptosis, and decreasing autophagic damage in myocardial cells [121], [122], [123], [124], [125], [126]. Hypoxia-inducible factor-1α (HIF-1α) regulates various angiogenic factors, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). Recent studies have demonstrated that exosomes derived from MSCs with overexpression of HIF-1α can mediate cardiac protection and angiogenesis through the aforementioned angiogenic factors [127]. After ischemia–reperfusion injury, myocardial tissue shows elevated expression of high-mobility group box 1 (HMGB1). Exosomes rich in miR-129-5p derived from bone marrow-derived mesenchymal stem cells (BMMSCs) can inhibit the expression of HMGB1 and inflammatory factors, improving mouse cardiac function and providing a novel approach for myocardial infarction treatment [128]. Exosomal miR-671 derived from adipose-derived mesenchymal stem cells (ADMSCs) can specifically inhibit the crucial receptor TGFBR2 in the TGF-β signaling pathway. This leads to the downregulation of SMAD2 phosphorylation, alleviating myocardial damage caused by myocardial infarction [128]. Exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) can target and inhibit the expression of divalent metal transporter 1 (DMT1) through miR-23a-3p, suppressing the process of ferroptosis and mitigating myocardial damage [123].

Exosomes derived from mesenchymal stem cells (MSCs) hold promising prospects in the treatment of post-myocardial infarction inflammation, promotion of angiogenesis, and anti-fibrosis [129], [130], [131]. However, the therapeutic efficacy of MSCs-Exo alone is limited, making it crucial to investigate methods to enhance MSCs-Exo effectiveness [132]. Pre-treatment of exosomes derived from bone marrow mesenchymal stem cells (BMMSCs) with fibronectin type III domain-containing protein 5 (FNDC5) has shown better therapeutic effects on infarcted hearts compared to exosomes from untreated BMMSCs. The mechanism involves inhibiting the NF-κB signaling pathway to reduce inflammation and promoting the nuclear translocation of transcription factor Nrf2, activating the expression of the antioxidant stress gene HO-1 [133]. The cytokine IFN-γ can improve myocardial infarction by upregulating the expression of miR-21 in MSC-Exos through the promotion of STAT1, facilitating angiogenesis, and reducing myocardial cell apoptosis [134]. Hemoglobin chloride can induce the expression of heme oxygenase-1, which has various cell-protective effects. Pre-treatment with it enhances the expression of miR-183-5p in exosomes secreted by MSCs. These exosomes protect myocardial cells by inhibiting the HMGB1/ERK pathway, thereby enhancing the potential for cardiac function restoration [135]. Similarly, exosomes secreted by umbilical cord mesenchymal stem cells (ucMSCs) genetically modified with macrophage migration inhibitory factor (MIF) enhance the promotion of angiogenesis, inhibition of apoptosis, reduction of fibrosis, and protection of cardiac function by upregulating the AKT signaling pathway mediated by miR-133a-3p [136]. It has been observed that pre-treatment of MSC-Exos with atorvastatin (ATV) upregulates the expression of long non-coding RNA (lncRNA) H19. This upregulation induces higher expression of miR-675, vascular endothelial growth factor (VEGF), and intercellular adhesion molecule-1 (ICAM-1), promoting angiogenesis and restoring cardiac function [137]. Interleukin 1 receptor-associated kinase 1 (IRAK1) is a crucial molecule involved in the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signal cascade, participating in the activation of the NF-κB inflammatory signaling pathway [138]. A study revealed that exosomes derived from MSCs treated with the traditional Chinese medicine Tongxinluo (MSCs TXL-Exo) significantly upregulate the expression of miR-146a-5p. Subsequently, miR-146a-5p downregulates the expression of IRAK1, reducing inflammation and apoptosis in myocardial cells after infarction and promoting myocardial repair [139].

2.2.3. Other stem cell-derived exosomes

Exosomal miR-294 secreted by embryonic stem cells (ESCs) can promote the proliferation and survival of cardiac repair-related cells, such as cardiac progenitor cells. The delivery of these exosomes to the myocardium can unleash the myocardial repair potential of ESCs through a non-cellular approach [140]. Adipose-derived stem cells (ADSCs) have advantages such as easy acquisition, less painful collection process, and no loss of differentiation potential during the expansion process, making them highly promising for cellular therapy in cardiovascular diseases [141]. Recent research results indicate that exosomes derived from ADSCs, highly expressing miR-205 under hypoxic conditions, can reduce myocardial cell apoptosis and inhibit myocardial fibrosis. Exosomal miR-196a-5p and miR-425-5p from ADSCs have also been proven to prevent myocardial cell apoptosis caused by mitochondrial dysfunction, promote macrophage polarization towards an anti-inflammatory phenotype, and facilitate angiogenesis, playing a crucial role in the multicellular repair response after myocardial infarction [142]. Exosomal miR-31 derived from ADSCs can downregulate the expression of the inhibitory factor for hypoxia-inducible factor-1 (FIH1), thereby activating hypoxia-inducible factor-1α (HIF-1α) and promoting angiogenesis [143]. The above research results suggest that ADSC-derived exosomes (ADSC-Exos) have significant development potential in the clinical treatment of myocardial infarction [144].

2.2.4. Endothelial cell-derived exosomes

Research has found that in IL-10 knockout (IL-10 KO) mice, endothelial progenitor cell-derived exosomes (IL-10KO-EPC-Exo) are highly enriched with integrin-linked kinase (ILK), which can activate the NF-κB pro-inflammatory signaling pathway, impair myocardial function, and subsequently affect the process of vascular regeneration [145]. A study by Wei Liu and colleagues found that exosomes derived from umbilical vein endothelial cells can significantly improve cardiac function after acute myocardial infarction and inhibit myocardial cell apoptosis; this protective effect may be achieved through the activation of the PI3K/AKT signaling pathway [146].

2.2.5. Cardiomyocyte-derived exosomes

Previous studies have confirmed that exosomes rich in miR-30a released by hypoxic myocardial cells can regulate autophagy in other myocardial cells by inhibiting the expression of autophagy-related proteins such as Beclin-1, representing a novel regulatory mechanism of post-ischemic myocardial autophagy. This may provide a basis for new therapeutic targets for ischemic heart disease, but further validation of this pathway's role in vivo is needed [147]. Research by Lei Wang and Jun Zhang reveals that hypoxic conditions upregulate the expression of lncRNA AK139128 in myocardial cells and their secreted exosomes. This can mediate apoptosis and inhibit the proliferation of cardiac fibroblasts, contributing to myocardial damage under hypoxic conditions [148]. Exosomes derived from myocardial cells containing miR-19-3p maintain elevated levels after myocardial infarction (MI). This miRNA can target the 3′-UTR of HIF-1α, reducing its expression and subsequently decreasing angiogenesis. Administration of anti-miR-19-3p (antagomiR-19a-3p) can counteract this process and promote angiogenesis after MI [149]. Another study reports a novel interstitial cell group in the heart called telocytes (CT). Exosomes derived from these cells, containing miR-21-5p, can target and inhibit the gene Cdip1, a downstream molecule of p53-dependent apoptosis. This downregulation attenuates the Caspase 3-mediated cell apoptosis process, promoting angiogenesis after myocardial infarction [150].

2.2.6. Therapeutic and clinical perspectives related to exosomes in myocardial infarction

In the past two decades, cell transplantation therapy after myocardial infarction has been extensively studied. However, recent data from the large-scale clinical trial PreSERVE-AMI involving bone marrow cell therapy in heart disease patients revealed that, despite the absence of safety issues, it failed to achieve the primary efficacy endpoint. This further confirms the suboptimal effectiveness of such cell therapies [151]. Limitations such as the immunogenicity of cells, tumorigenic risks, potential disruptions to cardiac electrical signals leading to arrhythmias, and low engraftment rates have restricted the application of this type of cell therapy [152]. Addressing these issues, Lei Ye and colleagues, for the first time, used a combination of human-induced pluripotent stem cell (hiPSC)-derived cardiovascular cell populations (cardiomyocytes, endothelial cells, and smooth muscle cells) with 3D fibrous patches for implantation into damaged myocardial tissue in a pig model of myocardial infarction. They found that the implantation of these three cell types significantly improved cardiac function post-infarction without inducing ventricular arrhythmias, demonstrating the reparative potential of hiPSC-derived cells for infarcted cardiac tissue [153]. Although cell therapy has shown initial efficacy, the difficulty in preserving cell products compared to traditional drugs and their impracticality for home use remain challenges. Based on this, Hao Li and colleagues utilized a pig myocardial infarction model to compare the therapeutic effects of a mixture of hiPSC-derived cardiovascular cells, corresponding cell fragments, and cell-released exosomes. The results showed that, compared to the infarct-only group, all three treatment approaches significantly improved cardiac function and reduced infarct damage, with comparable effectiveness. Notably, the therapeutic effect of exosomes was equivalent to that of transplanted cells but demonstrated easier storage and transportability, making it more promising for clinical translation [154].

Higher concentrations of calcium ions within cells are absorbed by mitochondria, leading to mitochondrial calcium overload, disrupting cellular energy metabolism, and promoting apoptosis [155]. Specifically, protein phosphatase 1 (PP1) is a serine/threonine dephosphorylation enzyme that removes phosphate groups from proteins. Its catalytic subunit, PP-1β, is responsible for executing the dephosphorylation reaction. When protein phosphatase inhibits the highly phosphorylated state of phospholamban (PLB), its inhibitory effect on the sarco/endoplasmic reticulum Ca2 + -ATPase (SERCA) pump in the sarcoplasmic reticulum diminishes. This leads to the imbalance of calcium homeostasis in cardiac cells, initiating pathways for myocardial apoptosis or damage [156]. Hao Li and colleagues discovered that extracellular vesicles secreted by endothelial cells derived from human induced pluripotent stem cells are rich in miR-100-5p, which selectively inhibits the expression and activity of PP-1β. This reduction in PP-1β activity decreases the dephosphorylation of PLB, maintaining the phosphorylation status of PLB and thereby protecting cardiac cells [157]. These research findings offer a cell-free therapeutic option for cardiac repair post-myocardial infarction.

So far, multiple research teams have developed various methods for delivering exosomes to damaged cardiac tissues post-myocardial infarction. For instance, Jianping Yuan and colleagues utilized gelatin microneedle patches loaded with anti-fibrotic miR-29b exosomes, implanted into the infarcted myocardium of mice, demonstrating effects in reducing inflammation, minimizing infarct size, inhibiting fibrosis, and improving cardiac function [158]. David J. Lundy's team has developed a porous scaffold with good biocompatibility that allows slow degradation in vivo, encapsulating therapeutic cells such as cardiac mesenchymal cells and enabling them to release exosomes, significantly enhancing the therapeutic effects of myocardial infarction [159]. Dashuai Zhu and colleagues, in rodent and pig models, demonstrated the safety and efficacy of intrapericardial injection of a hydrogel containing exosomes derived from mesenchymal stem cells, confirming that intrapericardial injection of therapeutic exosomes is a safe and effective method for cardiac repair [160]. The use of antibody-coupled magnetic nanoparticles to capture CD63-expressing exosomes, released in the acidic environment created in damaged myocardial tissue, has been confirmed to reduce infarct size and improve cardiac function in rabbits and rats [161]. Other research teams have developed a minimally invasive exosome spray (EXOS) and conducted experiments in mouse models of myocardial infarction, demonstrating its effectiveness in improving cardiac function and reducing myocardial fibrosis progression [162]. Furthermore, research teams have combined mesenchymal stem cell-derived exosomes with hydrogels to enhance the treatment of acute myocardial infarction [163], encapsulated therapeutic exosomes in iron oxide nanovesicles for magnetic-guided repair of injured cardiac tissue [164], and utilized nanofiber matrices to encapsulate active exosomes [165]. These developments provide more options for exosome-based treatments for myocardial infarction.

3. Cardiac ischemia–reperfusion injury

3.1. Introduction to cardiac ischemia–reperfusion injury

Acute myocardial infarction (AMI), as a disease with significant health threats, leads to a rapid decrease in blood flow to the nourishing myocardium, causing extensive myocardial cell necrosis. In severe cases, it can even result in cardiac arrest, contributing to a high global mortality rate [166]. Timely restoration of blood supply to the heart is considered crucial for maximizing cardiac function and improving prognosis [167]. However, during the process of reperfusion, additional myocardial damage occurs due to ischemia–reperfusion injury (IRI), resulting from abnormal inflammatory reactions, excessive oxidative stress levels, mitochondrial dysfunction, and various forms of cell death [168].

After cardiac reperfusion, the accumulated succinate during the ischemic phase is rapidly oxidized by succinate dehydrogenase (SDH). Meanwhile, complex I of the mitochondria undergoes reverse electron transfer (RET), generating an excess of reactive oxygen species (ROS), including superoxide anions. The excessive ROS, along with calcium overload, leads to the opening of the mitochondrial permeability transition pore (mPTP), resulting in myocardial cell death [169]. The gp130-JAK-STAT signaling pathway can directly act on myocardial cells, reducing myocardial cell apoptosis and protecting the heart from ischemia-reperfusion injury [170]. Exosomes derived from neural stem cells can protect the heart from ischemia-reperfusion injury. This is achieved by delaying the opening of the mitochondrial permeability transition pore (mPTP) through the mediation of the gp130-JAK/STAT pathway and its downstream effects [171]. Therefore, it is crucial to elucidate how exosomes participate in the mechanisms of myocardial ischemia–reperfusion injury.

3.2. Relationship between exosomes of different cellular origins and cardiac ischemia–reperfusion injury

3.2.1. Circulating exosomes

Chenkai Hu and colleagues, after ischemia–reperfusion modeling in mice, extracted exosomes from mouse serum and found an increased expression of miR-155-5p in I/R-Exos. This miRNA can negatively regulate the expression of NEDD4 protein, a member of the E3 ubiquitin ligase family, thereby inhibiting CyPD ubiquitination degradation and promoting ischemia–reperfusion injury [172]. In contrast, Jose M Vicencio and colleagues isolated exosomes from the blood of healthy adults and rats to assess the protective effects and mechanisms of plasma exosomes on ischemia–reperfusion myocardium. They found that the surface heat shock protein 70 (HSP70) on plasma exosomes can activate myocardial TLR4-mediated ERK1/2 and p38MAPK signaling pathways, induce HSP27 phosphorylation, and exert myocardial protection by preventing oxidation, resisting apoptosis, and maintaining sarcomere structure [96].

It is widely acknowledged that regular and moderate physical exercise is beneficial in reducing risk factors for cardiovascular diseases and can also alleviate myocardial ischemia–reperfusion injury [173]. Previous studies have confirmed the involvement of Caspase 9 and Jnk2 in inducing the process of cell apoptosis. A recent research report indicates the presence of protective signaling exosomes in the circulation of long-term exercisers, assisting in combating myocardial IRI. Mechanistically, exosomal miR-342-5p derived from long-term exercise not only targets Caspase 9 and Jnk2-induced myocardial cell apoptosis [174], [175] but also targets and inhibits the phosphatase gene Ppm1f (involved in dephosphorylation), enhancing the survival signal (p-Akt) [176]. This study proposes a novel mechanism for the protective effects of exercise on the cardiovascular system and emphasizes the potential of miR-342-5p in the prevention and treatment of cardiovascular diseases.

3.2.2. Immune cell-derived exosomes

Exosomes rich in miR-148a secreted by M2 macrophages can selectively inhibit the expression of Thioredoxin interacting protein (TXNIP) involved in oxidative stress, suppress the activation of downstream TLR4/NF-κB/NLRP3 pathway, alleviate inflammatory factor release, and mitigate inflammasome-mediated cardiomyocyte pyroptosis. Simultaneously, these exosomes can modulate the protein expression levels of IP3R and SERCA2a, reducing calcium overload and protecting the myocardium from ischemia-reperfusion injury [177].

The calcium-sensing receptor (CaSR) in the G protein-coupled receptor family has been demonstrated to participate in various inflammatory responses. Activation of CaSR in polymorphonuclear neutrophils (PMN) promotes the release of exosomes, which stimulate the expression of platelet-derived growth factor D (PDGFD) in cardiac myocytes and alleviate myocardial ischemia–reperfusion injury through the Akt signaling pathway [178].

3.2.3. Mesenchymal stem cell-derived exosomes

Research by Jinxuan Zhao and colleagues found that exosomes secreted by MSCs containing miR-182-5p can promote M2 polarization of macrophages after myocardial ischemia–reperfusion injury by inhibiting Toll-like receptor 4 (TLR4)-mediated oxidative stress and inflammatory response, thereby alleviating myocardial damage [179]. Similarly, exosomes secreted by MSCs enriched with miR-125a-5p can promote the aggregation of M2 macrophages, exerting anti-inflammatory effects. Additionally, they can inhibit fibroblast proliferation, reduce inflammation, and improve the survival of myocardial cells by promoting angiogenesis [23]. Furthermore, exosomes secreted by MSCs can carry and transfer miR-181a, targeting and inhibiting the expression of inflammation-related transcription factor c-Fos. This inhibition of the inflammatory response promotes the development and activation of Tregs, exerting a myocardial protective effect [180]. Moreover, cell pyroptosis, a process involving cell membrane rupture, mitochondrial swelling, and endoplasmic reticulum disruption, mediated by the gasdermin family, has received considerable attention in recent years [181]. Exosomes secreted by MSCs enriched with miR-320b can inhibit the expression of inflammatory pyroptosis-related proteins NLRP3 and Caspase-1, thereby reducing inflammation, protecting the myocardium from ischemia-reperfusion injury, and providing a basis for a novel treatment for ischemic heart disease [182]. In addition to exerting anti-inflammatory effects and reducing cell pyroptosis, research has reported that miR-143-3p in MSC-Exos can inhibit autophagic responses in myocardial ischemia–reperfusion injury by suppressing the CHK2/Beclin 1 pathway, thereby reducing cell apoptosis [183].

Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) play a role in reducing myocardial injury in ischemia–reperfusion injury through various pathways. One study reported that exosomes derived from BMSCs, containing the lncRNA HAND2-AS1, function as a molecular sponge to competitively bind to miR-17-5p and negatively regulate it. This leads to an increase in the expression of the downstream mitochondrial fusion protein (Mfn2), thereby maintaining mitochondrial morphology and function, reducing oxidative stress, and mitigating inflammation, ultimately reducing myocardial ischemia–reperfusion injury [184]. Another study suggested that lncRNA HCP5 (HLA complex P5) in hBMSC-Exos acts as a molecular sponge for miR-497, relieving the inhibitory effect of miR-497 on insulin-like growth factor 1 (IGF1). This leads to a reduction in myocardial cell damage [185], [186]. Stress or inflammation activates the c-Jun NH2-terminal kinase (JNK) pathway, also known as the stress-activated protein kinase (SAPK), which is an important member of the MAPK superfamily [187]. The activity of JNK is cascade-activated by upstream protein kinases MEKK1 and MKK4 (also known as SEK1). Previous studies have demonstrated that the MEKK1/MKK4/JNK signaling pathway can mediate caspase-dependent cell death [188]. Recent research indicates that miR-455-3p in BMSC-Exos can block the MEKK1/MKK4/JNK signaling pathway, inhibiting cell death and death-related autophagy to alleviate myocardial ischemia–reperfusion injury [189]. Additionally, miR-183-5p in BSMC-Exos can improve oxidative stress and apoptosis levels in myocardial cells during I/R by targeting and inhibiting the expression of Forkhead transcription factor (FOXO1), thereby ameliorating ischemia–reperfusion injury [190].

3.2.4. Fibroblast-derived exosomes

Recent studies have found that cardiac fibroblasts (CFs) have a protective effect on the heart during ischemia–reperfusion (I/R). The mechanism involves exosomal miR-133a derived from CFs, which targets and inhibits the expression of the pro-inflammatory protein ELAV-like RNA-binding protein 1 (ELAVL1) in cardiac myocytes, thereby suppressing myocardial cell pyroptosis and alleviating cardiac IRI [191], [192]. Postconditioning refers to a brief interruption of circulation in the early stages of reperfusion after percutaneous coronary intervention to open obstructed vessels, creating cycles of opening and closing, thereby mitigating reperfusion injury [193]. Postconditioning can promote the release of exosomes enriched with miR-423-3p from cardiac fibroblasts, exerting a protective effect on myocardial cells by downregulating RAP2C expression [194].

3.2.5 Exosomes from other cellular sources

Exosomes derived from cardiac progenitor cells (CPCs) are rich in miR-451, which can protect the myocardium from ischemia-reperfusion injury [195]. Exosomal miR-486-5p derived from bone marrow stromal cells can rescue myocardial ischemia–reperfusion injury by inhibiting PTEN expression and activating the PI3K/Akt signaling pathway to reduce cell apoptosis [196]. Cortical bone stem cells (CBSC), also known as marrow-derived stem cells, when directly injected into the infarcted area of mouse or pig myocardial infarction models, increase angiogenesis at the infarct border and partially restore heart function [197]. Further investigation by the research team revealed that exosomes secreted by CBSCs can recapitulate the anti-fibrotic and myocardial protective effects of CBSCs. This may be achieved by regulating the protein translation process mediated by snoRNA to inhibit fibroblast activation, providing a basis for the application of CBSC exosomes in the treatment of myocardial ischemic diseases [198].

3.3. Therapeutic and clinical perspectives related to exosomes in cardiac ischemia–reperfusion injury

Multiple studies have confirmed that Tanshinone IIA (TSA) is clinically applied in ischemia–reperfusion injury, exerting effects in reducing myocardial injury area and improving heart function [199], [200]. Recent research has confirmed that TSA treatment enhances the content of miR-223-5p in MSC-secreted exosomes, which can inhibit the activation of the CC chemokine receptor 2 (CCR2) signaling pathway on monocyte surfaces, alleviate monocyte myocardial infiltration, promote angiogenesis, thus significantly improving ischemic myocardial injury and function. The clinical application of Oridonin is achieved through its enhancement of autophagic activation in exosomes derived from bone marrow mesenchymal stem cells, exerting a protective effect on the heart [201].

In recent years, there has been rapid development of biomaterials in the treatment of myocardial infarction and ischemia–reperfusion (I/R), contributing to the restoration of the structure and function of the heart [202]. Researchers have designed an injectable hydrogel anchored with conductive properties derived from umbilical cord mesenchymal stem cell-derived exosomes. This hydrogel is relatively easy to obtain for standardized production [203], lacks potential tumorigenicity, exhibits prolonged retention at the site of application [204], and reduces the risk of arrhythmias caused by injection, providing a promising therapeutic approach for the treatment of heart I/R [205].

4. Heart failure

4.1. Introduction to heart failure

Heart failure typically results from the heart's inability to pump blood effectively, leading to insufficient perfusion of organs throughout the body. Since its classification as a global epidemic in 1997, heart failure has afflicted over 23 million people worldwide, making it a major public health concern [206], [207]. The treatment options for heart failure are diverse, encompassing not only traditional pharmacotherapy and cardiac rehabilitation measures but also emerging techniques like stem cell implantation. Furthermore, current research suggests that extracellular vesicles during reperfusion are believed to play a therapeutic role in the process of heart failure. Therefore, understanding more mechanisms of heart failure and exploring new treatment modalities is crucial [208].

4.2. Relationship between exosomes of different cellular origins and heart failure Fig. 3

4.2.1. Circulating exosomes

Chronic inflammation plays a crucial role in the development of heart failure [209]. So far, multiple studies have indicated an increase in the number and overactivation of peripheral blood mononuclear cells (PBMCs) in heart failure patients, promoting the release of inflammatory factors such as IL-10, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-alpha (TNF-α), thereby accelerating the progression of heart failure [210], [211]. A recent study pointed out that extracellular vesicles derived from healthy donor plasma (HDPE) when applied ex vivo to peripheral blood mononuclear cells (PBMCs) from chronic heart failure (CHF) patients, can decrease the expression of miRNA–126. This regulates the paracrine secretion of CHF patient PBMCs, reducing the release of inflammatory factors and exhibiting a protective effect on the heart [212].

In recent years, sympathetic hyperactivity induced by neuroinflammation has been shown to play a crucial role in the development of chronic heart failure [213]. Early sympathetic nerve activation serves a compensatory role, but prolonged and sustained hyperactivity can lead to severe adverse outcomes associated with heart failure [214]. The rostral ventrolateral medulla (RVLM) is a region located in the medullary part of the brainstem, playing a crucial role in regulating the cardiovascular system and being closely associated with the occurrence and development of heart failure [215]. Previous studies have indicated that in the RVLM, the enhancement of neuroinflammatory responses through the phosphatidylinositol 3-kinase (PI3K) signaling pathway contributes to increased sympathetic outflow in hypertensive patients [216]. Interestingly, while peripheral inflammatory stimuli can enhance inflammatory responses in the RVLM, peripheral inflammatory factors cannot directly affect the RVLM due to the blood–brain barrier (BBB) [217]. In this context, exosomes play a crucial role as a bridge for communication between the central and peripheral systems [218]. As described in a recent study, exosomes in the peripheral circulation containing miR-214-3p can enhance inflammatory responses, while let-7g-5p and let-7i-5p attenuate neuroinflammation. Heart failure (HF) patients can influence central inflammatory responses by regulating the expression of circulating exosomes [219]. Therefore, monitoring changes in circulating exosomes is helpful for researchers to identify targeted therapeutic strategies for heart failure.

4.2.2. Mesenchymal stem cell-derived exosomes

Mesenchymal stem cells (MSCs) are a type of multipotent stem cells derived from various tissues and organs such as bone marrow, adipose tissue, and muscles [220]. MSCs can protect the heart through mechanisms such as inhibiting inflammation, suppressing cell apoptosis, and promoting myocardial angiogenesis [221]. Some studies have demonstrated that MSCs face challenges such as low survival rates, high risk of tumor formation, host inability to generate immune tolerance, difficulties in tissue targeting, and preservation and transportation issues [222], [223]. Interestingly, researchers have discovered that MSCs can exert protective and reparative effects on the heart by secreting exosomes, showcasing powerful therapeutic potential. Consequently, MSC-Exos are extensively studied as an alternative to MSCs [224]. Previous studies have confirmed the role of MSC-Exos in providing cardiac protection and treatment [23]. Interestingly, a recent study indicates that adiponectin secreted by adipocytes can stimulate the secretion of exosomes from MSCs, thereby amplifying the therapeutic effects of MSC-Exos on heart failure [225]. Specifically, Thrombospondin-1 (TSP-1), a cell adhesion molecule with a Glycosylphosphatidylinositol (GPI) anchor, interacts with adiponectin in the plasma within the heart and vascular endothelium. This interaction promotes the occurrence and secretion of exosomes, thus amplifying the therapeutic effects of MSC-Exos [226]. Therefore, selectively inducing the production of adiponectin, such as by activating Peroxisome Proliferator-Activated Receptor γ (PPARγ), which is a major mediator of adiponectin production, is a promising therapeutic strategy [227].

In patients with heart failure, myocardial cells typically exhibit abnormal hypertrophy. At this stage, the increased energy demand of hypertrophic myocardial cells, coupled with microvascular dysfunction, leads to an imbalance in myocardial blood supply and oxygen, highlighting the importance of promoting vascular generation in preventing and treating chronic heart failure [228]. Previous studies have demonstrated that serine proteinase (PRSS23) can induce the Snail protein-mediated endothelial-to-mesenchymal transition (EndMT) process [229]. A recent study suggests that exosomal miR-1246 derived from human umbilical cord mesenchymal stem cells (hucMSCs) can selectively inhibit PRSS23, block the Snail signaling pathway, and consequently suppress the expression of the endothelial cell marker CD31, achieving the effect of promoting vascular generation [230]. Fibroblast growth factor 2 (FGF2) has been proven to be a vascular growth factor that promotes angiogenesis by interacting with Fibroblast Growth Factor Receptor 1 (FGFR1). However, the specific mechanism of the FGF/FGFR signaling axis in angiogenesis remains unclear [231], [232].

4.2.3. Other stem cell-derived exosomes

Doxorubicin (DOX), a widely used anthracycline anticancer agent, has gained attention due to its effective anticancer properties, but the associated cardiotoxicity has become a growing concern [233]. Due to the vulnerability and limited regenerative capacity of myocardial cells, the long-term use of DOX can lead to myocardial disease, left ventricular dysfunction, and ultimately result in heart failure [234]. Recent studies indicate that trophoblast stem cell-derived exosomes (TSC-Exos) can alleviate DOX-induced myocardial damage, rescuing the process through two mechanisms [235]. Specifically, TSC-Exos downregulates the expression of pro-apoptotic mediator miR-200b, and increases the expression of anti-apoptotic mediator E-cadherin transcriptional inhibitory factor Zeb1, reducing cardiomyocyte apoptosis. Additionally, TSC-Exos can block the NF-κB inflammatory signaling pathway activated by DOX, inhibiting inflammation [235]. DOX can upregulate the transcription factor FoxO1, which targets the promoter of the mitochondrial fusion protein (Mfn2), reducing Mfn2 expression and decreasing mitochondrial fusion. Promoting mitochondrial fusion can effectively reduce glycolysis and enhance the oxidative phosphorylation process, alleviating myocardial damage caused by reactive oxygen species (ROS) [236]. Recent studies suggest that TSC-Exos are involved in the activation of Mfn2 expression, contributing to the improvement of cardiac function [237]. Additionally, studies have reported that exosomes derived from embryonic stem cells (ESCs) are highly enriched in FGF2 protein, promoting myocardial angiogenesis to alleviate transverse aortic constriction (TAC)-induced heart failure, offering a new therapeutic option for heart failure patients [238].

4.2.4. Cardiomyocyte-derived exosomes

Myocardial fibrosis induced by pressure overload (PO) is a common scarring event involving fibroblast activation [239]. Excessive scar tissue (pathological remodeling) renders the myocardium stiff and impairs normal contractile and diastolic functions, ultimately leading to heart failure [239]. Recent studies indicate that downregulation of phosphatase and tension homolog (PTEN) expression or inhibition of the transforming growth factor-beta (TGF-β)/small mother against decapentaplegic (SMAD) signaling pathway can reduce myocardial fibrosis and improve cardiac function [240], [241]. Peli1, an E3 ubiquitin ligase, has been previously implicated in mediating the activation of fibroblasts (CFs) by TGF-β1 in past studies [242]. A recent study suggests that Peli1 can induce cardiomyocytes (CM) to produce exosomes rich in miR-494-3p. Subsequently, miR-494-3p activates CFs by inhibiting PTEN and amplifying phosphorylation processes of Akt, SMAD2/3, and ERK, promoting the fibrotic process in the heart [243]. Furthermore, the study mentions the use of recombinant adeno-associated virus serotype 9 (rAAV9), a gene interference vector, to deliver the inhibition of miR-494-3p in cardiac muscle. This approach significantly improves myocardial fibrosis, presenting a potential clinical therapeutic strategy for heart failure fibrosis [243]. Similarly, exosomes derived from Cardiosphere-derived cells (CDCs) have a rescuing effect on acute heart failure induced by pressure overload (PO), offering a novel therapeutic approach for clinical myocardial injury [244].

4.2.5. Therapeutic and clinical perspectives related to exosomes in heart failure

Severe fibrosis often occurs after myocardial infarction (MI), which is a crucial factor leading to heart failure and death. Therefore, the development of strategies to prevent and treat post-MI fibrosis is of great importance [245]. Microneedle (MN) patches, with excellent biocompatibility, can deliver bioactive substances in a painless and transdermal manner, achieving therapeutic effects for diseases [246]. Recent research has attempted to combine extracellular vesicles from human umbilical cord mesenchymal stem cells (HucMSCs) containing miR-29b with MN. Implanting them into the infarcted area of the myocardium can inhibit the TGF-β/Smad3 signaling pathway in cardiac fibroblasts (CFs), thereby reducing the degree of cardiac fibrosis [158], [247].

Previous studies have found that in patients with severe multivessel coronary artery disease requiring coronary artery bypass grafting (CABG), ischemic preconditioning (IPC) can protect the heart from myocardial injury and cardiomyocyte death caused by ischemia–reperfusion injury (IRI) [248]. IPC involves alternating short periods of ischemia and reperfusion, making the heart resistant to long-term ischemic damage [249]. However, the effectiveness of IPC in patients with heart failure is not evident [250]. However, recent research has proposed a novel treatment strategy. Exosomes produced after IPC in normal rats, when transferred to rats with heart failure, exhibit the ability to confer protection against IRI. These exosomes are rich in pro-survival enzymes and exert a protective effect on the heart through the phosphorylation of downstream ERK and AKT, offering a new avenue for addressing ischemic injury in patients with concurrent chronic heart failure [251].

Previous studies have indicated that using exosomes as carriers for delivering nucleic acids or drugs is a promising choice for targeted therapy. However, these therapeutic exosomes are prone to preferential uptake by the liver and spleen in the body, a consequence of the mononuclear phagocyte system's phagocytic activity, significantly limiting the clinical application of exosomes [252]. In recent research, Zhuo Wan and colleagues discovered that, before administering therapeutic exosomes with treatment effects, pre-injecting exosomes loaded with small interfering RNA (siRNA) targeting clathrin heavy chain (Cltc) enables subsequent distribution of therapeutic exosomes in target organs. This represents a promising gene therapy approach [253].

5. Cardiomyopathy

5.1. Introduction to diabetic cardiomyopathy

Diabetic cardiomyopathy (DCM) is a clinical complication of diabetes characterized by myocardial hypertrophy, fibrosis, and diastolic dysfunction [254]. The early manifestation of diabetic cardiomyopathy primarily involves impaired left ventricular diastolic function, while left ventricular systolic function and ejection fraction are generally normal. With disease progression, left ventricular hypertrophy and fibrosis intensify, ultimately leading to a decline in left ventricular systolic function, manifested by a decrease in ejection fraction. In summary, the course of diabetic cardiomyopathy evolves from diastolic dysfunction to systolic impairment [255]. Autophagy is the process of clearing damaged organelles and debris from the cytoplasm [256]. Numerous studies have demonstrated the downregulation of mitochondrial autophagy in DCM, and inducing autophagy in diabetic animal models can significantly reduce myocardial cell apoptosis and improve cardiac function [257], [258]. However, some studies suggest that excessive activation of autophagy may also accelerate the pathological process of DCM [259], [260], which could be attributed to variations in the modeling methods of diabetic animals in different experiments.

5.2. Relationship between exosomes of different cellular origins and diabetic cardiomyopathy

The heat shock response is a widely recognized intrinsic defense mechanism of cells [261]. Among the heat shock protein family, Hsp20 is the only Hsp that responds to both acute and chronic elevation of blood glucose. Research by Xiaohong Wang and colleagues reveals that Hsp20 interacts with the upstream factor Tsg101, involved in the exosome biogenesis pathway, promoting the generation of cardioprotective exosomes and providing protection against diabetic cardiomyopathy [262]. Furthermore, the research team found that under high glucose conditions, exosomes released by wild-type mouse cardiac cells have a detrimental effect on cardiac function. However, in transgenic mice with myocardial cell-specific overexpression of Hsp20, these harmful exosomes undergo “reprogramming” and transform into exosomes with protective effects, improving cardiac function under high glucose conditions [262]. Therefore, engineering exosomes with Hsp20 may be a novel therapeutic approach for diabetic cardiomyopathy.

An increasing number of studies have found that the interaction between the anti-apoptotic protein Bcl-2 and Beclin1 can inhibit the process of autophagy by preventing the dissociation of Beclin1 from class III phosphatidylinositol 3-kinase (PI3K) [263], [264], [265]. The Bax protein can also bind to Bcl-2, and the weakening of this binding restores the active conformation of Bax, thereby enhancing apoptosis. Activation of AMPK causes the separation of Bcl-2 and Beclin1, allowing Beclin1 to rebind with class III phosphatidylinositol 3-kinase (PI3K) and activate autophagy [266]. Mammalian sterile 20-like kinase 1 (MST1), a serine/threonine protein kinase, has been recently found in the study to be released by cardiac microvascular endothelial cells (CMECs) in exosomes. MST1 inhibits AMPK phosphorylation, thereby suppressing autophagy and promoting apoptosis, exacerbating diabetic cardiomyopathy [267]. Macrophage RNA-binding protein (HuR) is an RNA-binding protein that can bind to target mRNA, regulating its translation and stability. Previous studies have demonstrated that IL-10 can inhibit HuR expression, alleviating myocardial remodeling induced by myocardial infarction [268]. Recent research proposes that diabetes can stimulate the activity of macrophage HuR and transfer HuR to cardiac fibroblasts via exosomes, promoting inflammation and cardiac fibrosis. Therefore, targeting HuR may serve as a potential new strategy to limit cardiac fibrosis in diabetic patients [269].

AMPK is a serine/threonine protein kinase involved in regulating various metabolic processes in the heart. Additionally, it participates in autophagy activation by directly phosphorylating ULK1 at the Ser556 site, responsible for initiating autophagy [270]. In a diabetic rat model established using a high-fat, high-sugar diet and streptozotocin (STZ), it was found that exosomes derived from human umbilical cord mesenchymal stem cells (HUCMSC-EXO) can inhibit the AMPK-ULK1 signaling pathway, suppressing autophagy and improving cardiac function in DCM patients [271]. Similarly, in a rat model of diabetic myocardial injury, research revealed that exosomes derived from mesenchymal stem cells can also inhibit the TGF-β1/Smad2 signaling pathway, rescuing myocardial damage induced by high glucose [272].

5.3. Introduction to other types of cardiomyopathy and relationship to exosomes

5.3.1. Relationship between exosomes of different cellular origins and DOX-induced cardiomyopathy

The chemotherapeutic drug doxorubicin (DOX) exhibits strong cardiotoxicity, while miR-199a-3p in MSC-Exos can regulate the Akt-Sp1/p53 signaling pathway, upregulating the expression of survivin and Bcl-2 to exert a protective effect against DOX-induced cardiomyopathy [273]. Similarly, exosomes derived from cardiac progenitor cells (CPC) can selectively inhibit genes encoding inflammatory and cell death mediators (such as Traf6, Smad4, Irak1, Nox4, and Mpo), reducing oxidative stress damage and cardiomyocyte death induced by DOX [274].

5.3.2. Relationship between exosomes of different cellular origins and viral myocarditis

So far, scientists have identified six serotypes of Coxsackievirus B, among which Coxsackievirus B3 (CVB3) is a virus that specifically infects the myocardium and is considered a major pathogen of viral myocarditis [275]. Coxsackievirus B3 (CVB3)-induced viral myocarditis (VMC) is a myocardial disease characterized by inflammation, injury, and degeneration of non-ischemic myocardial cells [276]. Studies have shown that adipose-derived mesenchymal stem cell (ADSC)-derived exosomes can be transferred and engulfed by macrophages. The active STAT3 in exosomes can promote M2 polarization of macrophages, exerting anti-inflammatory and repair functions [277]. Another study demonstrates that HucMSC-Exos can upregulate the expression of autophagy-related proteins such as microtubule-associated protein light chain 3 (LC3), activating AMPK/mTOR-mediated autophagic flux. Simultaneously, it increases the expression of the anti-apoptotic protein Bcl-2, inhibiting cardiomyocyte apoptosis and improving cardiac function [278]. To further investigate the pathogenesis of myocarditis, researchers used an experimental autoimmune myocarditis (EAM) model and found that exosomes selectively expressing high levels of miR-142 in the EAM circulation could selectively inhibit the methylation-CpG binding domain protein 2 (MBD2)-mediated glycolysis, promoting CD4 + T cell activation and proliferation. Simultaneously, miR-142 could selectively inhibit the cytokine signal transducer inhibitor 1 (SOCS1), activating the JAK/STAT signaling pathway, and promoting CD4 + T cell inflammation. These parallel pathways contribute to the development of myocarditis [279].

5.3.3. Relationship between exosomes of different cellular origins and other types of cardiomyopathy

The pathogenic mechanisms of diseases such as obesity-related cardiomyopathy and Duchenne muscular dystrophy-related cardiomyopathy have also been investigated [280], [281]. A study by Yongshun Wang et al. first demonstrated that liver-secreted exosomal miR-122, by inhibiting the expression of mitochondrial protein ADP-ribosylation factor-like 2 in cardiomyocytes, impairs mitochondrial function and participates in the development of metabolic cardiomyopathy [280]. Similarly, another study revealed that liver-secreted exosomes rich in miR-29a are involved in the development of obesity-related cardiomyopathy. An inhibitor of miR-29a can counteract this damage and improve cardiac pathology [282].

5.4. Therapeutic and clinical perspectives of exosomes associated with cardiomyopathy

Although previous literature has demonstrated that exosomes released by cardiovascular cells can achieve intercellular communication by transporting miRNA, proteins, and cytokines, some challenges remain before applying exosomes in the clinic. For example, although multiple studies have validated the potential effects of exosome miRNAs in treating cardiomyopathy, only a few studies have thoroughly investigated the specific roles of miRNA cargos in the pathogenesis of cardiomyopathy. Therefore, a more comprehensive systematic analysis is critical to determine the key role of extracellular vesicles as therapeutic targets in cardiomyopathy.

Application of exosomes as biomarkers in cardiovascular diseases

Given the widespread presence of exosomes in various bodily fluids, they are widely regarded as potential biomarkers for many diseases. Therefore, theoretically, the identification of RNA in these exosomes can be employed to elucidate the unique characteristics of their host cells for diagnostic purposes. Exosomes have emerged as potential biomarkers for pre-diagnosis of diseases, with one approach being the monitoring of exosome levels in bodily fluids. Exosomes hold potential applications in early diagnosis, targeted therapy, prognosis, and clinical monitoring. We have summarized research on exosomes as biomarkers for cardiovascular disease diagnosis in the following Table 1.

Table 1.

Exosomes as diagnostic markers in cardiovascular disease.

Exosomes	Source	Disease	Exo Isolation	Exo Characterization	Quantification Methods	Clinical outcomes	Reference
miR-30d-5p miR-126a-5plncRNA LOC107986997lncRNA HIF1A-AS1	Plasma	Diabetic heart failure with preserved ejection fraction （HFpEF）	Ultracentrifugation	Transmission Electron Microscope（TEM）/ Nanoparticle tracking analysis (NTA) /Western Blot	Quantitative real-time polymerase chain reaction (qRT-PCR)	exosomes miR-30d and miR126a are associated with a significant reduction in cardiac output	[289]
	Serum	Atrial fibrillation（AF）	ExoQuick Exosome Precipitation kit	TEM/NTA/Western Blot	qRT-PCR	Expression levels of serum exosomes lncRNA LOC107986997 are strongly associated with persistent AF	[290]
	Plasma	Atherosclerosis（AS）	Ultracentrifugation	TEM/ Western Blot/ Flow Cytometry	qRT-PCR	Overexpression of circulating exosomes lncRNA HIF1A-AS1 may be caused by activation of endothelial cells and vascular smooth muscle cells	[291]
SOCS2-AS1	Plasma	Coronary heart disease（CAD）	Invitrogen™ Total Exosome Isolation Kit	–	qRT-PCR	Plasma exosome-encapsulated SOCS2-AS1 is a CAD-independent protective factor	[292]

lncRNAs ENST00000556899.1 ENST00000575985.1	Plasma	Acute myocardial infarction（AMI）	commercial kit (Qiagen Inc)	TEM/NTA/Western Blot	qRT-PCR	Circulating exosomes lncRNA ENST00000556899.1 and ENST00000575985.1 are elevated in patients with AMI	[293]
miR-122-5p	Plasma	Postoperative atrial fibrillation（POAF）	Ultracentrifugation	TEM/NTA/Western Blot	qRT-PCR	miR-122-5p can affect atrial function and structure, oxidative stress, and fibrosis involved in POAF progression	[294]
miRNA-382-3p miRNA-432-5p miRNA-200a-3p miRNA-3613-3p miRNA-125a-5p miRNA-185-5p miRNA-151a-3p miRNA-328-3p	Plasma	CAD	Ultracentrifugation	Western Blot/ Flow Cytometry	Illumina Next-Generation Sequencing	Exosomes upregulated in CAD miRNA:miRNA-382-3p miRNA-432-5p miRNA-200a-3p miRNA-3613-3p Down-regulated exosomes in CAD miRNA:miRNA-125a-5p miRNA-185-5p miRNA-151a-3p miRNA-328-3p	[295]
miR-942-5p miR-149-5p miR-32-5p	Serum	Stable coronary artery disease（SCAD）	ExoQuick® ULTRA EV Isolation Kit (SBI)	TEM/NTA/Western Blot	qRT-PCR	miR-942-5p, miR-149-5p and miR-32-5p can be used as novel diagnostic biomarkers for SCAD	[296]
hsa_circ_0005540	Plasma	CAD	exoRNeasy Serum/Plasma Midi kit (Qiagen)	–	qRT-PCR	Exosome cyclic RNA hsa_circ_0005540 as a novel diagnostic marker for CAD	[297]

Open in a new tab

Summary and outlook

Cardiovascular disease is a leading cause of death worldwide, claiming the lives of nearly 18 million people each year. In recent years, exosomes have garnered significant attention in the study of cardiovascular diseases due to their biocompatibility. This review provides a comprehensive summary of current research on the role of exosomes in various cardiovascular diseases, including heart failure, atherosclerosis, myocardial infarction, ischemia–reperfusion injury, and cardiomyopathy. Exosomes derived from cardiovascular cells, such as cardiomyocytes, endothelial cells, and stem cells, have been found to transport bioactive substances and participate in the cardioprotective and/or post-injury regenerative systems of cardiovascular tissues. Additionally, our review suggests that exosomes can serve as clinical diagnostic markers for cardiovascular disease, providing information on prognosis and disease progression. Overall, this review offers valuable insights into the potential therapeutic targets for the clinical treatment of cardiovascular diseases.

While exosome therapeutics have demonstrated efficacy, targeted delivery of exosomes remains a challenge. To address this issue, scientists have developed various biotechnologies to improve delivery efficiency and therapeutic effectiveness. For instance, cardiac homing peptides are utilized to target exosomes to cardiomyocytes for the treatment of myocardial infarction [283]. Additionally, recent studies have shown that exosomes can be increased using sonication, extrusion, electroporation, and novel click chemistry methods. Cargo can also be loaded into exosomes to enhance delivery efficiency [284]. Previous studies have shown that biological patches can effectively deliver drugs to the heart, aiding in heart repair and regeneration [285], [286]. However, the use of surgical thoracotomy to implant heart patches can be problematic for patients with mild to moderate HF, often leading to complications such as pericardial adhesions [287]. To address this issue, researchers have developed a new method called intrapericardial injection (iPC), which involves injecting a thermosensitive hydrogel containing induced pluripotent stem cell-derived cardiac progenitor cells (iPS-CPC) or MSC-Exos directly into the pericardial cavity. This results in the formation of a lamellar structure that achieves a therapeutic effect, while avoiding the need for surgical intervention [160]. Another study utilized MSC-Exos combined with hyaluronic acid hydrogel to create an injectable ExoGel, which has shown promising results in treating HF patients [288]. These two methods have significant potential for treating mild to moderate HF due to their ability to be highly retained in the heart, weak immune response, and non-invasive nature. Further development of technologies involving exosomes is necessary for early application in clinical treatment.

Funding Statement

This study was supported by the National Natural Science Foundation of China (82171571, 82171572, 81970254, 82100302, 82301778, 82102740, 82073647, 82373674, 32300987), the Science Foundation for Outstanding Youth of Liaoning Province (2023JH3/10200017), and the Shenyang Youth Science and Technology Innovation Talent Support Program (RC210076, RC210078).

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

Biographies

Yixiao Zhang, M.D., Associate Professor, Deputy Chief Physician of urological surgical department, Shengjing Hospital of China Medical University. In the past five years, we have authored and published 15 SCI papers, serving as either the first author or corresponding author. These publications collectively possess a cumulative impact factor of 175.9, with the highest individual impact factor reaching an impressive 37.3. Furthermore, five of these papers have achieved an SCI impact factor exceeding 10 points.

Guozhe Sun, is an Associate Chief Physician and Associate Professor in Cardiology at the First Hospital of China Medical University. With a doctoral degree, he specializes in clinical and interventional treatment of coronary heart disease, angina, myocardial infarction, and heart failure. Dr. Sun is the Deputy Director of the Cardiovascular Department, a national coronary intervention training mentor, and honored with the Liaoning Province Science and Technology Progress Award. With over 10 years of coronary intervention experience, he has conducted 3,000+ procedures, excelling in complex cases. Dr. Sun has authored 14 SCI papers, led research projects, and has rich clinical expertise in cardiovascular diseases.

Xingang Zhang, Associate Chief Physician and Associate Professor in the Department of Cardiology at the First Hospital of China Medical University, holds a doctoral degree. Specializing in cardiovascular epidemiology and interventional cardiology, he excels in the diagnosis and treatment of diseases such as coronary heart disease, ventricular septal defect, atrial septal defect, aortic stenosis, angina, myocardial infarction, ischemic cardiomyopathy, and dilated cardiomyopathy. Dr. Zhang actively contributes to hypertension and stroke prevention projects in rural China and has published extensively in prestigious medical journals. He has received multiple awards for his research achievements, including first prizes at the provincial and national levels. Dr. Zhang is also involved in key cardiovascular disease observation initiatives in rural areas of China.

graphic file with name fx1.jpg

Zhaobo Zhang, Born in 1999, the First Hospital of China Medical University, 2022-09 - Present, China Medical University, Internal Medicine, Master's Degree.

graphic file with name fx11.jpg

Ying Zhang, Professor, Doctoral Supervisor, Doctor of Biology, Department of Cardiovascular Medicine, The First Hospital of China Medical University. In the past five years, we have published 20 SCI papers as the first author (or corresponding author), with a cumulative impact factor of 224.508, the highest single impact factor of 44.1, three SCI impact factors greater than 20 points, and seven greater than 10 points.

graphic file with name fx10.jpg

Yingxian Sun, National Second Class Professor, Doctoral Supervisor, Director of the Department of Cardiovascular Medicine of the First Affiliated Hospital of China Medical University, Director of the Cardiovascular Research Institute of China Medical University, Academic Leader of Internal Medicine. He has published a total of 310 SCI papers as the first/corresponding author, with a total IF=1197 and the highest single IF=202.

graphic file with name fx9.jpg

Naijin Zhang is a professor, Ph.D. supervisor, and MD in the Department of Cardiovascular Medicine at the First Affiliated Hospital of China Medical University. In the past five years, we have tabulated 36 SCI papers as the first author (or corresponding author), with a cumulative impact factor of 317.371, the highest single impact factor of 44.1, three SCI impact factors greater than 20 points, and seven greater than 10 points.

graphic file with name fx2.jpg

Yuanming Zou, born in 1997, the First Hospital of China Medical University, Ph.D. student, 2020-09 to present China Medical University, Internal Medicine, Ph.D. student, participated in two National Natural Science Foundation of China (NSFC) projects in the past five years.

graphic file with name fx3.jpg

Song Chunyu, Born in 1998, the First Hospital of China Medical University, Master's Degree, 2021-09 to present China Medical University, Master's Degree, Internal Medicine

graphic file with name fx4.jpg

Cao Kexin, Born in 1996, the First Hospital of China Medical University, Master's Degree, China Medical University, Master's Degree in Internal Medicine, China Medical University, 2021-09 – Present

graphic file with name fx8.jpg

Danxi Geng, born in 1996, the First Hospital of China Medical University, PhD Candidate, 2019-09 to present China Medical University, Internal Medicine, PhD Candidate.

graphic file with name fx6.jpg

Shuxian Chen, Born in 1999, the First Hospital of China Medical University, 2022-09 - Present, China Medical University, Internal Medicine, Master's Degree.

graphic file with name fx5.jpg

Kexin Cai, Born in 1999, the First Hospital of China Medical University, China, 2022-09 - Present, China Medical University, Internal Medicine, Master's Degree.

graphic file with name fx7.jpg

Yanjiao Wu, Born in 1999, the First Hospital of China Medical University, 2022-09 - Present, China Medical University, Internal Medicine, Master's Degree.

Contributor Information

Guozhe Sun, Email: gzhsun66@163.com.

Naijin Zhang, Email: njzhang@cmu.edu.cn.

Xingang Zhang, Email: zhangxingang80@aliyun.com.

Yixiao Zhang, Email: zhangyx201@hotmail.com.

Yingxian Sun, Email: yxsun@cmu.edu.cn.

Ying Zhang, Email: yzhang02@cmu.edu.cn.

References

1.YáñEZ-Mó M, Siljander PR, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions [J]. J. Extracell. Vesicles, 2015, 4: 27066. [DOI] [PMC free article] [PubMed]
2.Wang C., Li Z., Liu Y., et al. Exosomes in atherosclerosis: performers, bystanders, biomarkers, and therapeutic targets [J] Theranostics. 2021;11(8):3996–4010. doi: 10.7150/thno.56035. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Kalluri R, Lebleu V S. The biology, function, and biomedical applications of exosomes [J]. Science (New York, NY), 2020, 367(6478). [DOI] [PMC free article] [PubMed]
4.Kalluri R. The biology and function of exosomes in cancer [J] J Clin Invest. 2016;126(4):1208–1215. doi: 10.1172/JCI81135. [DOI] [PMC free article] [PubMed] [Google Scholar]
5.Wen S.W., Lima L.G., Lobb R.J., et al. Breast cancer-derived exosomes reflect the cell-of-origin phenotype [J] Proteomics. 2019;19(8):e1800180. doi: 10.1002/pmic.201800180. [DOI] [PubMed] [Google Scholar]
6.Han L., Lam E.W., Sun Y. Extracellular vesicles in the tumor microenvironment: old stories, but new tales [J] Mol Can. 2019;18(1):59. doi: 10.1186/s12943-019-0980-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
7.Lao K.H., Zeng L., Xu Q. Endothelial and smooth muscle cell transformation in atherosclerosis [J] Curr Opin Lipidol. 2015;26(5):449–456. doi: 10.1097/MOL.0000000000000219. [DOI] [PubMed] [Google Scholar]
8.Liu Q., Piao H., Wang Y., et al. Circulating exosomes in cardiovascular disease: Novel carriers of biological information [J] Biomed pharmacotherapy = Biomed pharmacotherapie. 2021;135 doi: 10.1016/j.biopha.2020.111148. [DOI] [PubMed] [Google Scholar]
9.Zhao D., Liu J., Wang M., et al. Epidemiology of cardiovascular disease in China: current features and implications [J] Nat Rev Cardiol. 2019;16(4):203–212. doi: 10.1038/s41569-018-0119-4. [DOI] [PubMed] [Google Scholar]
10.van Niel G., D'Angelo G., Raposo G. Shedding light on the cell biology of extracellular vesicles [J] Nat Rev Mol Cell Biol. 2018;19(4):213–228. doi: 10.1038/nrm.2017.125. [DOI] [PubMed] [Google Scholar]
11.Lai JJ, Chau ZL, Chen SY, et al. Exosome processing and characterization approaches for research and technology development [J]. Adv Sci (Weinheim, Baden-Wurttemberg, Germany), 2022, 9(15): e2103222. [DOI] [PMC free article] [PubMed]
12.Anakor E., le Gall L., Dumonceaux J., et al. Exosomes in ageing and motor neurone disease: biogenesis, uptake mechanisms, modifications in disease and uses in the development of biomarkers and therapeutics [J] Cells. 2021;10(11) doi: 10.3390/cells10112930. [DOI] [PMC free article] [PubMed] [Google Scholar]
13.Kamerkar S., Lebleu V.S., Sugimoto H., et al. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer [J] Nature. 2017;546(7659):498–503. doi: 10.1038/nature22341. [DOI] [PMC free article] [PubMed] [Google Scholar]
14.Hanayama R., Tanaka M., Miwa K., et al. Identification of a factor that links apoptotic cells to phagocytes [J] Nature. 2002;417(6885):182–187. doi: 10.1038/417182a. [DOI] [PubMed] [Google Scholar]
15.Saunderson S.C., Dunn A.C., Crocker P.R., et al. CD169 mediates the capture of exosomes in spleen and lymph node [J] Blood. 2014;123(2):208–216. doi: 10.1182/blood-2013-03-489732. [DOI] [PMC free article] [PubMed] [Google Scholar]
16.Segura E., Nicco C., Lombard B., et al. ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming [J] Blood. 2005;106(1):216–223. doi: 10.1182/blood-2005-01-0220. [DOI] [PubMed] [Google Scholar]
17.Nolte-'T Hoen E N, Buschow S I, Anderton S M, et al. Activated T cells recruit exosomes secreted by dendritic cells via LFA-1 [J]. Blood, 2009;113(9):1977–81. [DOI] [PubMed]
18.Hakulinen J., Junnikkala S., Sorsa T., et al. Complement inhibitor membrane cofactor protein (MCP; CD46) is constitutively shed from cancer cell membranes in vesicles and converted by a metalloproteinase to a functionally active soluble form [J] Eur J Immunol. 2004;34(9):2620–2629. doi: 10.1002/eji.200424969. [DOI] [PubMed] [Google Scholar]
19.Tian T., Zhu Y.L., Zhou Y.Y., et al. Exosome uptake through clathrin-mediated endocytosis and macropinocytosis and mediating miR-21 delivery [J] J Biol Chem. 2014;289(32):22258–22267. doi: 10.1074/jbc.M114.588046. [DOI] [PMC free article] [PubMed] [Google Scholar]
20.Parton R.G., Tillu V.A., Collins B.M. Caveolae [J] Curr Biol. 2018;28(8):R402–R405. doi: 10.1016/j.cub.2017.11.075. [DOI] [PubMed] [Google Scholar]
21.El-Sayed A., Harashima H. Endocytosis of gene delivery vectors: from clathrin-dependent to lipid raft-mediated endocytosis [J] Mol Therapy: J. Am Soc Gene Therapy. 2013;21(6):1118–1130. doi: 10.1038/mt.2013.54. [DOI] [PMC free article] [PubMed] [Google Scholar]
22.Andreu Z., YáñEZ-Mó M. Tetraspanins in extracellular vesicle formation and function [J] Front Immunol. 2014;5:442. doi: 10.3389/fimmu.2014.00442. [DOI] [PMC free article] [PubMed] [Google Scholar]
23.Gao L., Qiu F., Cao H., et al. Therapeutic delivery of microRNA-125a-5p oligonucleotides improves recovery from myocardial ischemia/reperfusion injury in mice and swine [J] Theranostics. 2023;13(2):685–703. doi: 10.7150/thno.73568. [DOI] [PMC free article] [PubMed] [Google Scholar]
24.Raposo G., Nijman H.W., Stoorvogel W., et al. B lymphocytes secrete antigen-presenting vesicles [J] J Exp Med. 1996;183(3):1161–1172. doi: 10.1084/jem.183.3.1161. [DOI] [PMC free article] [PubMed] [Google Scholar]
25.Tabas I., Bornfeldt K.E. Macrophage phenotype and function in different stages of atherosclerosis [J] Circ Res. 2016;118(4):653–667. doi: 10.1161/CIRCRESAHA.115.306256. [DOI] [PMC free article] [PubMed] [Google Scholar]
26.Libby P., Loscalzo J., Ridker P.M., et al. Inflammation, immunity, and infection in atherothrombosis: JACC review topic of the week [J] J Am Coll Cardiol. 2018;72(17):2071–2081. doi: 10.1016/j.jacc.2018.08.1043. [DOI] [PMC free article] [PubMed] [Google Scholar]
27.Libby P. Inflammation in atherosclerosis-no longer a theory [J] Clin Chem. 2021;67(1):131–142. doi: 10.1093/clinchem/hvaa275. [DOI] [PubMed] [Google Scholar]
28.Libby P. The changing landscape of atherosclerosis [J] Nature. 2021;592(7855):524–533. doi: 10.1038/s41586-021-03392-8. [DOI] [PubMed] [Google Scholar]
29.Dzau V.J., Braun-Dullaeus R.C., Sedding D.G. Vascular proliferation and atherosclerosis: new perspectives and therapeutic strategies [J] Nat Med. 2002;8(11):1249–1256. doi: 10.1038/nm1102-1249. [DOI] [PubMed] [Google Scholar]
30.Libby P., Ridker P.M., Hansson G.K. Progress and challenges in translating the biology of atherosclerosis [J] Nature. 2011;473(7347):317–325. doi: 10.1038/nature10146. [DOI] [PubMed] [Google Scholar]
31.Davis G.E., Senger D.R. Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization [J] Circ Res. 2005;97(11):1093–1107. doi: 10.1161/01.RES.0000191547.64391.e3. [DOI] [PubMed] [Google Scholar]
32.Baruah J., Wary K.K. Exosomes in the regulation of vascular endothelial cell regeneration [J] Front Cell Dev Biol. 2019;7:353. doi: 10.3389/fcell.2019.00353. [DOI] [PMC free article] [PubMed] [Google Scholar]
33.Chen Y.T., Yuan H.X., Ou Z.J., et al. Microparticles (Exosomes) and atherosclerosis [J] Curr Atheroscler Rep. 2020;22(6):23. doi: 10.1007/s11883-020-00841-z. [DOI] [PubMed] [Google Scholar]
34.Heo J, Kang H. Exosome-Based Treatment for Atherosclerosis [J]. International journal of molecular sciences 2022;23(2). [DOI] [PMC free article] [PubMed]
35.Leroyer A.S., Isobe H., LESèCHE G., et al. Cellular origins and thrombogenic activity of microparticles isolated from human atherosclerotic plaques [J] J Am Coll Cardiol. 2007;49(7):772–777. doi: 10.1016/j.jacc.2006.10.053. [DOI] [PubMed] [Google Scholar]
36.Mallat Z., Hugel B., Ohan J., et al. Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity [J] Circulation. 1999;99(3):348–353. doi: 10.1161/01.cir.99.3.348. [DOI] [PubMed] [Google Scholar]
37.Tong X., Dang X., Liu D., et al. Exosome-derived circ_0001785 delays atherogenesis through the ceRNA network mechanism of miR-513a-5p/TGFBR3 [J] J Nanobiotechnol. 2023;21(1):362. doi: 10.1186/s12951-023-02076-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
38.Ding Z., Pothineni N.V.K., Goel A., et al. PCSK9 and inflammation: role of shear stress, pro-inflammatory cytokines, and LOX-1 [J] Cardiovasc Res. 2020;116(5):908–915. doi: 10.1093/cvr/cvz313. [DOI] [PubMed] [Google Scholar]
39.Ding J., Li H., Liu W., et al. miR-186-5p dysregulation in serum exosomes from patients with AMI aggravates atherosclerosis via targeting LOX-1 [J] Int J Nanomed. 2022;17:6301–6316. doi: 10.2147/IJN.S383904. [DOI] [PMC free article] [PubMed] [Google Scholar]
40.Hayden M.S., Ghosh S. Shared principles in NF-kappaB signaling [J] Cell. 2008;132(3):344–362. doi: 10.1016/j.cell.2008.01.020. [DOI] [PubMed] [Google Scholar]
41.Gilmore T.D. Introduction to NF-kappaB: players, pathways, perspectives [J] Oncogene. 2006;25(51):6680–6684. doi: 10.1038/sj.onc.1209954. [DOI] [PubMed] [Google Scholar]
42.Brasier A.R. The NF-kappaB regulatory network [J] Cardiovasc Toxicol. 2006;6(2):111–130. doi: 10.1385/ct:6:2:111. [DOI] [PubMed] [Google Scholar]
43.Perkins N.D. Integrating cell-signalling pathways with NF-kappaB and IKK function [J] Nat Rev Mol Cell Biol. 2007;8(1):49–62. doi: 10.1038/nrm2083. [DOI] [PubMed] [Google Scholar]
44.Zhu Z., Zhang G., Li D., et al. Silencing of specificity protein 1 protects H9c2 cells against lipopolysaccharide-induced injury via binding to the promoter of chemokine CXC receptor 4 and suppressing NF-κB signaling [J] Bioengineered. 2022;13(2):3395–3409. doi: 10.1080/21655979.2022.2026548. [DOI] [PMC free article] [PubMed] [Google Scholar]
45.Chan J., Prado-Lourenco L., Khachigian L.M., et al. TRAIL promotes VSMC proliferation and neointima formation in a FGF-2-, Sp1 phosphorylation-, and NFkappaB-dependent manner [J] Circ Res. 2010;106(6):1061–1071. doi: 10.1161/CIRCRESAHA.109.206029. [DOI] [PubMed] [Google Scholar]
46.Zheng B., Yin W.N., Suzuki T., et al. Exosome-mediated miR-155 transfer from smooth muscle cells to endothelial cells induces endothelial injury and promotes atherosclerosis [J] Mol Therapy: J Am Soc Gene Therapy. 2017;25(6):1279–1294. doi: 10.1016/j.ymthe.2017.03.031. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
47.Liu P., Wang S., Wang G., et al. Macrophage-derived exosomal miR-4532 promotes endothelial cells injury by targeting SP1 and NF-κB P65 signalling activation [J] J Cell Mol Med. 2022;26(20):5165–5180. doi: 10.1111/jcmm.17541. [DOI] [PMC free article] [PubMed] [Google Scholar]
48.DéLéRIS P, Bacqueville D, Gayral S, et al. SHIP-2 and PTEN are expressed and active in vascular smooth muscle cell nuclei, but only SHIP-2 is associated with nuclear speckles [J]. J Biol Chem 2003;278(40):38884-91. [DOI] [PubMed]
49.Pi S., Mao L., Chen J., et al. The P2RY12 receptor promotes VSMC-derived foam cell formation by inhibiting autophagy in advanced atherosclerosis [J] Autophagy. 2021;17(4):980–1000. doi: 10.1080/15548627.2020.1741202. [DOI] [PMC free article] [PubMed] [Google Scholar]
50.Sasaoka T., Kikuchi K., Wada T., et al. Dual role of SRC homology domain 2-containing inositol phosphatase 2 in the regulation of platelet-derived growth factor and insulin-like growth factor I signaling in rat vascular smooth muscle cells [J] Endocrinology. 2003;144(9):4204–4214. doi: 10.1210/en.2003-0190. [DOI] [PubMed] [Google Scholar]
51.Ren L., Chen S., Yao D., et al. OxLDL-stimulated macrophage exosomes promote proatherogenic vascular smooth muscle cell viability and invasion via delivering miR-186-5p then inactivating SHIP2 mediated PI3K/AKT/mTOR pathway [J] Mol Immunol. 2022;146:27–37. doi: 10.1016/j.molimm.2022.02.018. [DOI] [PubMed] [Google Scholar]
52.Babic M., Schuchardt M., TöLLE M., et al. In times of tobacco-free nicotine consumption: the influence of nicotine on vascular calcification [J] Eur J Clin Invest. 2019;49(4):e13077. doi: 10.1111/eci.13077. [DOI] [PubMed] [Google Scholar]
53.Wang Z., Liu B., Zhu J., et al. Nicotine-mediated autophagy of vascular smooth muscle cell accelerates atherosclerosis via nAChRs/ROS/NF-κB signaling pathway [J] Atherosclerosis. 2019;284:1–10. doi: 10.1016/j.atherosclerosis.2019.02.008. [DOI] [PubMed] [Google Scholar]
54.Moulton K.S., Li M., Strand K., et al. PTEN deficiency promotes pathological vascular remodeling of human coronary arteries [J] JCI insight. 2018;3(4) doi: 10.1172/jci.insight.97228. [DOI] [PMC free article] [PubMed] [Google Scholar]
55.Furgeson S.B., Simpson P.A., Park I., et al. Inactivation of the tumour suppressor, PTEN, in smooth muscle promotes a pro-inflammatory phenotype and enhances neointima formation [J] Cardiovasc Res. 2010;86(2):274–282. doi: 10.1093/cvr/cvp425. [DOI] [PMC free article] [PubMed] [Google Scholar]
56.Zhu J., Liu B., Wang Z., et al. Exosomes from nicotine-stimulated macrophages accelerate atherosclerosis through miR-21-3p/PTEN-mediated VSMC migration and proliferation [J] Theranostics. 2019;9(23):6901–6919. doi: 10.7150/thno.37357. [DOI] [PMC free article] [PubMed] [Google Scholar]
57.Bouchareychas L., Duong P., Covarrubias S., et al. Macrophage exosomes resolve atherosclerosis by regulating hematopoiesis and inflammation via MicroRNA Cargo [J] Cell Rep. 2020;32(2) doi: 10.1016/j.celrep.2020.107881. [DOI] [PMC free article] [PubMed] [Google Scholar]
58.Zhang S., Wang W., Wu X., et al. Regulatory roles of circular RNAs in coronary artery disease [J] Mol. Therapy Nucleic Acids. 2020;21:172–179. doi: 10.1016/j.omtn.2020.05.024. [DOI] [PMC free article] [PubMed] [Google Scholar]
59.Tong K.L., Tan K.E., Lim Y.Y., et al. CircRNA-miRNA interactions in atherogenesis [J] Mol Cell Biochem. 2022;477(12):2703–2733. doi: 10.1007/s11010-022-04455-8. [DOI] [PubMed] [Google Scholar]
60.Xiong F., Mao R., Zhang L., et al. CircNPHP4 in monocyte-derived small extracellular vesicles controls heterogeneous adhesion in coronary heart atherosclerotic disease [J] Cell Death Dis. 2021;12(10):948. doi: 10.1038/s41419-021-04253-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
61.Gao W., Liu H., Yuan J., et al. Exosomes derived from mature dendritic cells increase endothelial inflammation and atherosclerosis via membrane TNF-α mediated NF-κB pathway [J] J Cell Mol Med. 2016;20(12):2318–2327. doi: 10.1111/jcmm.12923. [DOI] [PMC free article] [PubMed] [Google Scholar]
62.Lin B., Xie W., Zeng C., et al. Transfer of exosomal microRNA-203-3p from dendritic cells to bone marrow-derived macrophages reduces development of atherosclerosis by downregulating Ctss in mice [J] Aging. 2021;13(11):15638–15658. doi: 10.18632/aging.103842. [DOI] [PMC free article] [PubMed] [Google Scholar]
63.Li J., Xue H., Li T., et al. Exosomes derived from mesenchymal stem cells attenuate the progression of atherosclerosis in ApoE(-/-) mice via miR-let7 mediated infiltration and polarization of M2 macrophage [J] Biochem Biophys Res Commun. 2019;510(4):565–572. doi: 10.1016/j.bbrc.2019.02.005. [DOI] [PubMed] [Google Scholar]
64.Ma J., Chen L., Zhu X., et al. Mesenchymal stem cell-derived exosomal miR-21a-5p promotes M2 macrophage polarization and reduces macrophage infiltration to attenuate atherosclerosis [J] Acta Biochim Biophy Sin. 2021;53(9):1227–1236. doi: 10.1093/abbs/gmab102. [DOI] [PubMed] [Google Scholar]
65.Xing X., Li Z., Yang X., et al. Adipose-derived mesenchymal stem cells-derived exosome-mediated microRNA-342-5p protects endothelial cells against atherosclerosis [J] Aging. 2020;12(4):3880–3898. doi: 10.18632/aging.102857. [DOI] [PMC free article] [PubMed] [Google Scholar]
66.Sun L., He X., Zhang T., et al. Knockdown of mesenchymal stem cell-derived exosomal LOC100129516 suppresses the symptoms of atherosclerosis via upregulation of the PPARγ/LXRα/ABCA1 signaling pathway [J] Int J Mol Med. 2021;48(6) doi: 10.3892/ijmm.2021.5041. [DOI] [PMC free article] [PubMed] [Google Scholar]
67.Silva-GARCÍA O, Valdez-Alarcón JJ, Baizabal-Aguirre VM. The Wnt/β-catenin signaling pathway controls the inflammatory response in infections caused by pathogenic bacteria [J]. Mediat Inflam 2014: 310183. [DOI] [PMC free article] [PubMed]
68.Gustafson B., Smith U. Cytokines promote Wnt signaling and inflammation and impair the normal differentiation and lipid accumulation in 3T3-L1 preadipocytes [J] J Biol Chem. 2006;281(14):9507–9516. doi: 10.1074/jbc.M512077200. [DOI] [PubMed] [Google Scholar]
69.Gao H., Yu Z., Li Y., et al. miR-100-5p in human umbilical cord mesenchymal stem cell-derived exosomes mediates eosinophilic inflammation to alleviate atherosclerosis via the FZD5/Wnt/β-catenin pathway [J] Acta Biochim Biophy Sin. 2021;53(9):1166–1176. doi: 10.1093/abbs/gmab093. [DOI] [PubMed] [Google Scholar]
70.Döring Y, Soehnlein O, Weber C. Neutrophil extracellular traps in atherosclerosis and atherothrombosis [J]. Circulat Res 2017;120(4):736-43. [DOI] [PubMed]
71.Chen L., Hu L., Li Q., et al. Exosome-encapsulated miR-505 from ox-LDL-treated vascular endothelial cells aggravates atherosclerosis by inducing NET formation [J] Acta Biochim Biophy Sin. 2019;51(12):1233–1241. doi: 10.1093/abbs/gmz123. [DOI] [PubMed] [Google Scholar]
72.Gao H., Wang X., Lin C., et al. Exosomal MALAT1 derived from ox-LDL-treated endothelial cells induce neutrophil extracellular traps to aggravate atherosclerosis [J] Biol Chem. 2020;401(3):367–376. doi: 10.1515/hsz-2019-0219. [DOI] [PubMed] [Google Scholar]
73.Zhang Y.G., Song Y., Guo X.L., et al. Exosomes derived from oxLDL-stimulated macrophages induce neutrophil extracellular traps to drive atherosclerosis [J] Cell cycle (Georgetown, Tex) 2019;18(20):2674–2684. doi: 10.1080/15384101.2019.1654797. [DOI] [PMC free article] [PubMed] [Google Scholar]
74.Galluzzi L., Green D.R. Autophagy-independent functions of the autophagy machinery [J] Cell. 2019;177(7):1682–1699. doi: 10.1016/j.cell.2019.05.026. [DOI] [PMC free article] [PubMed] [Google Scholar]
75.Guo F.X., Wu Q., Li P., et al. The role of the LncRNA-FA2H-2-MLKL pathway in atherosclerosis by regulation of autophagy flux and inflammation through mTOR-dependent signaling [J] Cell Death Differ. 2019;26(9):1670–1687. doi: 10.1038/s41418-018-0235-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
76.Ke X., Liao Z., Luo X., et al. Endothelial colony-forming cell-derived exosomal miR-21-5p regulates autophagic flux to promote vascular endothelial repair by inhibiting SIPL1A2 in atherosclerosis [J] Cell Commun Signal. 2022;20(1):30. doi: 10.1186/s12964-022-00828-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
77.van Gaal L.F., Mertens I.L., de Block C.E. Mechanisms linking obesity with cardiovascular disease [J] Nature. 2006;444(7121):875–880. doi: 10.1038/nature05487. [DOI] [PubMed] [Google Scholar]
78.Flaherty SE, 3RD, Grijalva A, Xu X, et al. A lipase-independent pathway of lipid release and immune modulation by adipocytes [J]. Science (New York, NY), 2019, 363(6430): 989-93. [DOI] [PMC free article] [PubMed]
79.Xie Z., Wang X., Liu X., et al. Adipose-derived exosomes exert proatherogenic effects by regulating macrophage foam cell formation and polarization [J] J Am Heart Assoc. 2018;7(5) doi: 10.1161/JAHA.117.007442. [DOI] [PMC free article] [PubMed] [Google Scholar]
80.Pan Y., Hui X., Hoo R.L.C., et al. Adipocyte-secreted exosomal microRNA-34a inhibits M2 macrophage polarization to promote obesity-induced adipose inflammation [J] J Clin Invest. 2019;129(2):834–849. doi: 10.1172/JCI123069. [DOI] [PMC free article] [PubMed] [Google Scholar]
81.Tang Y., Yang L.J., Liu H., et al. Exosomal miR-27b-3p secreted by visceral adipocytes contributes to endothelial inflammation and atherogenesis [J] Cell Rep. 2023;42(1) doi: 10.1016/j.celrep.2022.111948. [DOI] [PubMed] [Google Scholar]
82.Song Y., Li H., Ren X., et al. SNHG9, delivered by adipocyte-derived exosomes, alleviates inflammation and apoptosis of endothelial cells through suppressing TRADD expression [J] Eur J Pharmacol. 2020;872 doi: 10.1016/j.ejphar.2020.172977. [DOI] [PubMed] [Google Scholar]
83.Wang F., Chen F.F., Shang Y.Y., et al. Insulin resistance adipocyte-derived exosomes aggravate atherosclerosis by increasing vasa vasorum angiogenesis in diabetic ApoE(-/-) mice [J] Int J Cardiol. 2018;265:181–187. doi: 10.1016/j.ijcard.2018.04.028. [DOI] [PubMed] [Google Scholar]
84.Massberg S., Brand K., GRüNER S., et al. A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation [J] J Exp Med. 2002;196(7):887–896. doi: 10.1084/jem.20012044. [DOI] [PMC free article] [PubMed] [Google Scholar]
85.Huo Y., Schober A., Forlow S.B., et al. Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E [J] Nat Med. 2003;9(1):61–67. doi: 10.1038/nm810. [DOI] [PubMed] [Google Scholar]
86.Srikanthan S., Li W., Silverstein R.L., et al. Exosome poly-ubiquitin inhibits platelet activation, downregulates CD36 and inhibits pro-atherothombotic cellular functions [J] J Thrombosis Haemostasis: JTH. 2014;12(11):1906–1917. doi: 10.1111/jth.12712. [DOI] [PMC free article] [PubMed] [Google Scholar]
87.Li J., Tan M., Xiang Q., et al. Thrombin-activated platelet-derived exosomes regulate endothelial cell expression of ICAM-1 via microRNA-223 during the thrombosis-inflammation response [J] Thromb Res. 2017;154:96–105. doi: 10.1016/j.thromres.2017.04.016. [DOI] [PubMed] [Google Scholar]
88.Yao Y., Sun W., Sun Q., et al. Platelet-derived exosomal microRNA-25-3p inhibits coronary vascular endothelial cell inflammation through Adam10 via the NF-κB signaling pathway in ApoE(-/-) mice [J] Front Immunol. 2019;10:2205. doi: 10.3389/fimmu.2019.02205. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
89.Lahmann A.L., Joner M. In-stent restenosis: chasing our tails in search of a solution [J] JACC Basic Translat Sci. 2020;5(1):12–14. doi: 10.1016/j.jacbts.2019.12.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
90.Zou D., Yang P., Liu J., et al. Exosome-loaded pro-efferocytic vascular stent with Lp-PLA(2)-triggered release for preventing in-stent restenosis [J] ACS Nano. 2022;16(9):14925–14941. doi: 10.1021/acsnano.2c05847. [DOI] [PubMed] [Google Scholar]
91.Iyer D., Zhao Q., Wirka R., et al. Coronary artery disease genes SMAD3 and TCF21 promote opposing interactive genetic programs that regulate smooth muscle cell differentiation and disease risk [J] PLoS Genet. 2018;14(10):e1007681. doi: 10.1371/journal.pgen.1007681. [DOI] [PMC free article] [PubMed] [Google Scholar]
92.Gao X.F., Wang Z.M., Chen A.Q., et al. Plasma small extracellular vesicle-carried miRNA-501-5p promotes vascular smooth muscle cell phenotypic modulation-mediated in-stent restenosis [J] Oxid Med Cell Longev. 2021;2021:6644970. doi: 10.1155/2021/6644970. [DOI] [PMC free article] [PubMed] [Google Scholar]
93.Yan W., Li T., Yin T., et al. M2 macrophage-derived exosomes promote the c-KIT phenotype of vascular smooth muscle cells during vascular tissue repair after intravascular stent implantation [J] Theranostics. 2020;10(23):10712–10728. doi: 10.7150/thno.46143. [DOI] [PMC free article] [PubMed] [Google Scholar]
94.Thygesen K., Alpert J.S., Jaffe A.S., et al. Fourth universal definition of myocardial infarction (2018) [J] J Am Coll Cardiol. 2018;72(18):2231–2264. doi: 10.1016/j.jacc.2018.08.1038. [DOI] [PubMed] [Google Scholar]
95.Benjamin E.J., Muntner P., Alonso A., et al. Heart disease and stroke statistics-2019 update: a report from the American heart association [J] Circulation. 2019;139(10):e56–e528. doi: 10.1161/CIR.0000000000000659. [DOI] [PubMed] [Google Scholar]
96.JM V, DM Y, V S, et al. Plasma exosomes protect the myocardium from ischemia-reperfusion injury [J]. Journal of the American College of Cardiology, 2015, 65(15): 1525-36. [DOI] [PubMed]
97.Wang B., Cao C., Han D., et al. Dysregulation of miR-342-3p in plasma exosomes derived from convalescent AMI patients and its consequences on cardiac repair [J] Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2021;142 doi: 10.1016/j.biopha.2021.112056. [DOI] [PubMed] [Google Scholar]
98.Zhang Q., Wang L., Wang S., et al. Signaling pathways and targeted therapy for myocardial infarction [J] Signal Transduct Target Ther. 2022;7(1):78. doi: 10.1038/s41392-022-00925-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
99.Jeong H., Choi D., Oh Y., et al. A nanocoating co-localizing nitric oxide and growth factor onto individual endothelial cells reveals synergistic effects on angiogenesis [J] Adv Healthc Mater. 2022;11(6):e2102095. doi: 10.1002/adhm.202102095. [DOI] [PubMed] [Google Scholar]
100.Li H., Liao Y., Gao L., et al. Coronary serum exosomes derived from patients with myocardial ischemia regulate angiogenesis through the mir-939-mediated nitric oxide signaling pathway [J] Theranostics. 2018;8(8):2079–2093. doi: 10.7150/thno.21895. [DOI] [PMC free article] [PubMed] [Google Scholar]
101.El-Hashemite N., Walker V., Zhang H., et al. Loss of Tsc1 or Tsc2 induces vascular endothelial growth factor production through mammalian target of rapamycin [J] Can Res. 2003;63(17):5173–5177. [PubMed] [Google Scholar]
102.Rattner A., Williams J., Nathans J. Roles of HIFs and VEGF in angiogenesis in the retina and brain [J] J Clin Invest. 2019;129(9):3807–3820. doi: 10.1172/JCI126655. [DOI] [PMC free article] [PubMed] [Google Scholar]
103.Tian X., Liu Y., Wang Z., et al. miR-144 delivered by nasopharyngeal carcinoma-derived EVs stimulates angiogenesis through the FBXW7/HIF-1α/VEGF-A axis [J] Mol Therapy Nucl Acids. 2021;24:1000–1011. doi: 10.1016/j.omtn.2021.03.016. [DOI] [PMC free article] [PubMed] [Google Scholar]
104.Duan S., Wang C., Xu X., et al. Peripheral serum exosomes isolated from patients with acute myocardial infarction promote endothelial cell angiogenesis via the miR-126-3p/TSC1/mTORC1/HIF-1α pathway [J] Int J Nanomed. 2022;17:1577–1592. doi: 10.2147/IJN.S338937. [DOI] [PMC free article] [PubMed] [Google Scholar]
105.Li H., Ding J., Liu W., et al. Plasma exosomes from patients with acute myocardial infarction alleviate myocardial injury by inhibiting ferroptosis through miR-26b-5p/SLC7A11 axis [J] Life Sci. 2023;322 doi: 10.1016/j.lfs.2023.121649. [DOI] [PubMed] [Google Scholar]
106.Prabhu S.D., Frangogiannis N.G. The biological basis for cardiac repair after myocardial infarction: from inflammation to fibrosis [J] Circ Res. 2016;119(1):91–112. doi: 10.1161/CIRCRESAHA.116.303577. [DOI] [PMC free article] [PubMed] [Google Scholar]
107.Ma Y., Yabluchanskiy A., Lindsey M.L. Neutrophil roles in left ventricular remodeling following myocardial infarction [J] Fibrogenesis Tissue Repair. 2013;6(1):11. doi: 10.1186/1755-1536-6-11. [DOI] [PMC free article] [PubMed] [Google Scholar]
108.Xiong Y.Y., Gong Z.T., Tang R.J., et al. The pivotal roles of exosomes derived from endogenous immune cells and exogenous stem cells in myocardial repair after acute myocardial infarction [J] Theranostics. 2021;11(3):1046–1058. doi: 10.7150/thno.53326. [DOI] [PMC free article] [PubMed] [Google Scholar]
109.Zlatanova I., Pinto C., Bonnin P., et al. Iron regulator hepcidin impairs macrophage-dependent cardiac repair after injury [J] Circulation. 2019;139(12):1530–1547. doi: 10.1161/CIRCULATIONAHA.118.034545. [DOI] [PubMed] [Google Scholar]
110.Mouton A J, DELEON-Pennell K Y, Rivera Gonzalez O J, et al. Mapping macrophage polarization over the myocardial infarction time continuum [J]. Basic research in cardiology, 2018, 113(4): 26. [DOI] [PMC free article] [PubMed]
111.Liu S., Chen J., Shi J., et al. M1-like macrophage-derived exosomes suppress angiogenesis and exacerbate cardiac dysfunction in a myocardial infarction microenvironment [J] Basic Res Cardiol. 2020;115(2):22. doi: 10.1007/s00395-020-0781-7. [DOI] [PubMed] [Google Scholar]
112.Koh W., Mahan R.D., Davis G.E. Cdc42- and Rac1-mediated endothelial lumen formation requires Pak2, Pak4 and Par3, and PKC-dependent signaling [J] J Cell Sci. 2008;121(Pt 7):989–1001. doi: 10.1242/jcs.020693. [DOI] [PubMed] [Google Scholar]
113.Wang C., Zhang C., Liu L., et al. Macrophage-derived mir-155-containing exosomes suppress fibroblast proliferation and promote fibroblast inflammation during cardiac injury [J] Mol Therapy: J Am Soc Gene Therapy. 2017;25(1):192–204. doi: 10.1016/j.ymthe.2016.09.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
114.Long R., Gao L., Li Y., et al. M2 macrophage-derived exosomes carry miR-1271-5p to alleviate cardiac injury in acute myocardial infarction through down-regulating SOX6 [J] Mol Immunol. 2021;136:26–35. doi: 10.1016/j.molimm.2021.05.006. [DOI] [PubMed] [Google Scholar]
115.Ding J., Chen J., Wang Y., et al. Trbp regulates heart function through microRNA-mediated Sox6 repression [J] Nat Genet. 2015;47(7):776–783. doi: 10.1038/ng.3324. [DOI] [PMC free article] [PubMed] [Google Scholar]
116.Hu H., Wu J., Cao C., et al. Exosomes derived from regulatory T cells ameliorate acute myocardial infarction by promoting macrophage M2 polarization [J] IUBMB Life. 2020;72(11):2409–2419. doi: 10.1002/iub.2364. [DOI] [PubMed] [Google Scholar]
117.Zhu J., Yao K., Guo J., et al. miR-181a and miR-150 regulate dendritic cell immune inflammatory responses and cardiomyocyte apoptosis via targeting JAK1-STAT1/c-Fos pathway [J] J Cell Mol Med. 2017;21(11):2884–2895. doi: 10.1111/jcmm.13201. [DOI] [PMC free article] [PubMed] [Google Scholar]
118.Choo E.H., Lee J.H., Park E.H., et al. Infarcted myocardium-primed dendritic cells improve remodeling and cardiac function after myocardial infarction by modulating the regulatory T cell and macrophage polarization [J] Circulation. 2017;135(15):1444–1457. doi: 10.1161/CIRCULATIONAHA.116.023106. [DOI] [PubMed] [Google Scholar]
119.Liu H., Zhang Y., Yuan J., et al. Dendritic cell-derived exosomal miR-494-3p promotes angiogenesis following myocardial infarction [J] Int J Mol Med. 2021;47(1):315–325. doi: 10.3892/ijmm.2020.4776. [DOI] [PMC free article] [PubMed] [Google Scholar]
120.Li F., Wang Y., Lin L., et al. Mast cell-derived exosomes promote Th2 cell differentiation via OX40L-OX40 ligation [J] J Immunol Res. 2016;2016:3623898. doi: 10.1155/2016/3623898. [DOI] [PMC free article] [PubMed] [Google Scholar]
121.Peng Y., Zhao J.L., Peng Z.Y., et al. Exosomal miR-25-3p from mesenchymal stem cells alleviates myocardial infarction by targeting pro-apoptotic proteins and EZH2 [J] Cell Death Dis. 2020;11(5):317. doi: 10.1038/s41419-020-2545-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
122.Sun L., Zhu W., Zhao P., et al. Long noncoding RNA UCA1 from hypoxia-conditioned hMSC-derived exosomes: a novel molecular target for cardioprotection through miR-873-5p/XIAP axis [J] Cell Death Dis. 2020;11(8):696. doi: 10.1038/s41419-020-02783-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
123.Song Y., Wang B., Zhu X., et al. Human umbilical cord blood-derived MSCs exosome attenuate myocardial injury by inhibiting ferroptosis in acute myocardial infarction mice [J] Cell Biol Toxicol. 2021;37(1):51–64. doi: 10.1007/s10565-020-09530-8. [DOI] [PubMed] [Google Scholar]
124.Gong X.H., Liu H., Wang S.J., et al. Exosomes derived from SDF1-overexpressing mesenchymal stem cells inhibit ischemic myocardial cell apoptosis and promote cardiac endothelial microvascular regeneration in mice with myocardial infarction [J] J Cell Physiol. 2019;234(8):13878–13893. doi: 10.1002/jcp.28070. [DOI] [PubMed] [Google Scholar]
125.Mao Q., Liang X.L., Zhang C.L., et al. LncRNA KLF3-AS1 in human mesenchymal stem cell-derived exosomes ameliorates pyroptosis of cardiomyocytes and myocardial infarction through miR-138-5p/Sirt1 axis [J] Stem Cell Res Ther. 2019;10(1):393. doi: 10.1186/s13287-019-1522-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
126.Xiao C., Wang K., Xu Y., et al. Transplanted mesenchymal stem cells reduce autophagic flux in infarcted hearts via the exosomal transfer of miR-125b [J] Circ Res. 2018;123(5):564–578. doi: 10.1161/CIRCRESAHA.118.312758. [DOI] [PubMed] [Google Scholar]
127.Sun J., Shen H., Shao L., et al. HIF-1α overexpression in mesenchymal stem cell-derived exosomes mediates cardioprotection in myocardial infarction by enhanced angiogenesis [J] Stem Cell Res Ther. 2020;11(1):373. doi: 10.1186/s13287-020-01881-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
128.Wang S., Dong J., Li L., et al. Exosomes derived from miR-129-5p modified bone marrow mesenchymal stem cells represses ventricular remolding of mice with myocardial infarction [J] J Tissue Eng Regen Med. 2022;16(2):177–187. doi: 10.1002/term.3268. [DOI] [PubMed] [Google Scholar]
129.S B, L Z, L D, et al. Extracellular vesicles derived from human bone marrow mesenchymal stem cells promote angiogenesis in a rat myocardial infarction model [J]. J Mol Med (Berlin, Germany), 2014, 92(4): 387-97. [DOI] [PubMed]
130.Gao L., Mei S., Zhang S., et al. Cardio-renal exosomes in myocardial infarction serum regulate proangiogenic paracrine signaling in adipose mesenchymal stem cells [J] Theranostics. 2020;10(3):1060–1073. doi: 10.7150/thno.37678. [DOI] [PMC free article] [PubMed] [Google Scholar]
131.Liu D., Gu G., Gan L., et al. Identification of a CTRP9 C-Terminal polypeptide capable of enhancing bone-derived mesenchymal stem cell cardioprotection through promoting angiogenic exosome production [J] Redox Biol. 2021;41 doi: 10.1016/j.redox.2021.101929. [DOI] [PMC free article] [PubMed] [Google Scholar]
132.Hashemi S.M., Ghods S., Kolodgie F.D., et al. A placebo controlled, dose-ranging, safety study of allogenic mesenchymal stem cells injected by endomyocardial delivery after an acute myocardial infarction [J] Eur Heart J. 2008;29(2):251–259. doi: 10.1093/eurheartj/ehm559. [DOI] [PubMed] [Google Scholar]
133.Ning H., Chen H., Deng J., et al. Exosomes secreted by FNDC5-BMMSCs protect myocardial infarction by anti-inflammation and macrophage polarization via NF-κB signaling pathway and Nrf2/HO-1 axis [J] Stem Cell Res Ther. 2021;12(1):519. doi: 10.1186/s13287-021-02591-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
134.Zhang J., Lu Y., Mao Y., et al. IFN-γ enhances the efficacy of mesenchymal stromal cell-derived exosomes via miR-21 in myocardial infarction rats [J] Stem Cell Res Ther. 2022;13(1):333. doi: 10.1186/s13287-022-02984-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
135.Zheng H., Liang X., Han Q., et al. Hemin enhances the cardioprotective effects of mesenchymal stem cell-derived exosomes against infarction via amelioration of cardiomyocyte senescence [J] J Nanobiotechnol. 2021;19(1):332. doi: 10.1186/s12951-021-01077-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
136.Zhu W., Sun L., Zhao P., et al. Macrophage migration inhibitory factor facilitates the therapeutic efficacy of mesenchymal stem cells derived exosomes in acute myocardial infarction through upregulating miR-133a-3p [J] J Nanobiotechnol. 2021;19(1):61. doi: 10.1186/s12951-021-00808-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
137.Huang P., Wang L., Li Q., et al. Atorvastatin enhances the therapeutic efficacy of mesenchymal stem cells-derived exosomes in acute myocardial infarction via up-regulating long non-coding RNA H19 [J] Cardiovasc Res. 2020;116(2):353–367. doi: 10.1093/cvr/cvz139. [DOI] [PMC free article] [PubMed] [Google Scholar]
138.Su L.C., Xu W.D., Huang A.F. IRAK family in inflammatory autoimmune diseases [J] Autoimmun Rev. 2020;19(3) doi: 10.1016/j.autrev.2020.102461. [DOI] [PubMed] [Google Scholar]
139.Xiong Y., Tang R., Xu J., et al. Tongxinluo-pretreated mesenchymal stem cells facilitate cardiac repair via exosomal transfer of miR-146a-5p targeting IRAK1/NF-κB p65 pathway [J] Stem Cell Res Ther. 2022;13(1):289. doi: 10.1186/s13287-022-02969-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
140.M K, E N, T A, et al. Embryonic stem cell-derived exosomes promote endogenous repair mechanisms and enhance cardiac function following myocardial infarction [J]. Circulation research, 2015, 117(1): 52-64. [DOI] [PMC free article] [PubMed]
141.Mazini L., Rochette L., Amine M., et al. Regenerative capacity of adipose derived stem cells (ADSCs), comparison with mesenchymal stem cells (MSCs) [J] Int J Mol Sci. 2019;20(10) doi: 10.3390/ijms20102523. [DOI] [PMC free article] [PubMed] [Google Scholar]
142.DE ALMEIDA OLIVEIRA N C, NERI E A, SILVA C M, et al. Multicellular regulation of miR-196a-5p and miR-425-5 from adipose stem cell-derived exosomes and cardiac repair [J]. Clinical science (London, England : 1979), 2022, 136(17): 1281-301. [DOI] [PubMed]
143.Zhu D., Wang Y., Thomas M., et al. Exosomes from adipose-derived stem cells alleviate myocardial infarction via microRNA-31/FIH1/HIF-1α pathway [J] J Mol Cell Cardiol. 2022;162:10–19. doi: 10.1016/j.yjmcc.2021.08.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
144.Wang T., Li T., Niu X., et al. ADSC-derived exosomes attenuate myocardial infarction injury by promoting miR-205-mediated cardiac angiogenesis [J] Biol Direct. 2023;18(1):6. doi: 10.1186/s13062-023-00361-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
145.Yue Y., Wang C., Benedict C., et al. Interleukin-10 deficiency alters endothelial progenitor cell-derived exosome reparative effect on myocardial repair via integrin-linked kinase enrichment [J] Circ Res. 2020;126(3):315–329. doi: 10.1161/CIRCRESAHA.119.315829. [DOI] [PMC free article] [PubMed] [Google Scholar]
146.Liu W., Feng Y., Wang X., et al. Human umbilical vein endothelial cells-derived exosomes enhance cardiac function after acute myocardial infarction by activating the PI3K/AKT signaling pathway [J] Bioengineered. 2022;13(4):8850–8865. doi: 10.1080/21655979.2022.2056317. [DOI] [PMC free article] [PubMed] [Google Scholar]
147.Yang Y., Li Y., Chen X., et al. Exosomal transfer of miR-30a between cardiomyocytes regulates autophagy after hypoxia [J] J Mol Med (Berl) 2016;94(6):711–724. doi: 10.1007/s00109-016-1387-2. [DOI] [PubMed] [Google Scholar]
148.Wang L., Zhang J. Exosomal lncRNA AK139128 derived from hypoxic cardiomyocytes promotes apoptosis and inhibits cell proliferation in cardiac fibroblasts [J] Int J Nanomed. 2020;15:3363–3376. doi: 10.2147/IJN.S240660. [DOI] [PMC free article] [PubMed] [Google Scholar]
149.Gou L., Xue C., Tang X., et al. Inhibition of Exo-miR-19a-3p derived from cardiomyocytes promotes angiogenesis and improves heart function in mice with myocardial infarction via targeting HIF-1α [J] Aging. 2020;12(23):23609–23618. doi: 10.18632/aging.103563. [DOI] [PMC free article] [PubMed] [Google Scholar]
150.Liao Z., Chen Y., Duan C., et al. Cardiac telocytes inhibit cardiac microvascular endothelial cell apoptosis through exosomal miRNA-21-5p-targeted cdip1 silencing to improve angiogenesis following myocardial infarction [J] Theranostics. 2021;11(1):268–291. doi: 10.7150/thno.47021. [DOI] [PMC free article] [PubMed] [Google Scholar]
151.A futile cycle in cell therapy [J]. Nat Biotechnol, 2017, 35(4): 291. [DOI] [PubMed]
152.Yanamandala M., Zhu W., Garry D.J., et al. Overcoming the roadblocks to cardiac cell therapy using tissue engineering [J] J Am Coll Cardiol. 2017;70(6):766–775. doi: 10.1016/j.jacc.2017.06.012. [DOI] [PMC free article] [PubMed] [Google Scholar]
153.Ye L., Chang Y.H., Xiong Q., et al. Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cells [J] Cell Stem Cell. 2014;15(6):750–761. doi: 10.1016/j.stem.2014.11.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
154.Gao L., Wang Y., Wei P., Krishnamurthy G.P., Walcott P., Menasché J.Z. Erratum for the Research Article: “Exosomes secreted by hiPSC-derived cardiac cells improve recovery from myocardial infarction in swine” by L. [J] Sci Translat Med. 2020;12(567) doi: 10.1126/scitranslmed.aay1318. [DOI] [PubMed] [Google Scholar]
155.Gorski P.A., Ceholski D.K., Hajjar R.J. Altered myocardial calcium cycling and energetics in heart failure–a rational approach for disease treatment [J] Cell Metab. 2015;21(2):183–194. doi: 10.1016/j.cmet.2015.01.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
156.Aoyama H., Ikeda Y., Miyazaki Y., et al. Isoform-specific roles of protein phosphatase 1 catalytic subunits in sarcoplasmic reticulum-mediated Ca(2+) cycling [J] Cardiovasc Res. 2011;89(1):79–88. doi: 10.1093/cvr/cvq252. [DOI] [PubMed] [Google Scholar]
157.Li H., Wang L., Ma T., et al. Exosomes secreted by endothelial cells derived from human induced pluripotent stem cells improve recovery from myocardial infarction in mice [J] Stem Cell Res Ther. 2023;14(1):278. doi: 10.1186/s13287-023-03462-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
158.Yuan J., Yang H., Liu C., et al. Microneedle patch loaded with exosomes containing MicroRNA-29b prevents cardiac fibrosis after myocardial infarction [J] Adv Healthc Mater. 2023::e2202959. doi: 10.1002/adhm.202202959. [DOI] [PubMed] [Google Scholar]
159.Czosseck A., Chen M.M., Nguyen H., et al. Porous scaffold for mesenchymal cell encapsulation and exosome-based therapy of ischemic diseases [J] J Control Release. 2022;352:879–892. doi: 10.1016/j.jconrel.2022.10.057. [DOI] [PubMed] [Google Scholar]
160.Zhu D., Li Z., Huang K., et al. Minimally invasive delivery of therapeutic agents by hydrogel injection into the pericardial cavity for cardiac repair [J] Nat Commun. 2021;12(1):1412. doi: 10.1038/s41467-021-21682-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
161.Liu S., Chen X., Bao L., et al. Treatment of infarcted heart tissue via the capture and local delivery of circulating exosomes through antibody-conjugated magnetic nanoparticles [J] Nat Biomed Eng. 2020;4(11):1063–1075. doi: 10.1038/s41551-020-00637-1. [DOI] [PubMed] [Google Scholar]
162.Yao J., Huang K., Zhu D., et al. A minimally invasive exosome spray repairs heart after myocardial infarction [J] ACS Nano. 2021;15(7):11099–11111. doi: 10.1021/acsnano.1c00628. [DOI] [PubMed] [Google Scholar]
163.Hu X., Ning X., Zhao Q., et al. Islet-1 mesenchymal stem cells-derived exosome-incorporated angiogenin-1 hydrogel for enhanced acute myocardial infarction therapy [J] ACS Appl Mater Interfaces. 2022;14(32):36289–36303. doi: 10.1021/acsami.2c04686. [DOI] [PubMed] [Google Scholar]
164.Lee J.R., Park B.W., Kim J., et al. Nanovesicles derived from iron oxide nanoparticles-incorporated mesenchymal stem cells for cardiac repair [J] Sci Adv. 2020;6(18):eaaz0952. doi: 10.1126/sciadv.aaz0952. [DOI] [PMC free article] [PubMed] [Google Scholar]
165.Ping P., Guan S., Ning C., et al. Fabrication of blended nanofibrous cardiac patch transplanted with TGF-β3 and human umbilical cord MSCs-derived exosomes for potential cardiac regeneration after acute myocardial infarction [J] Nanomed Nanotechnol Biol Med. 2023;54 doi: 10.1016/j.nano.2023.102708. [DOI] [PubMed] [Google Scholar]
166.Kazemi Asl S, Rahimzadegan M, Ostadrahimi R. The recent advancement in the chitosan hybrid-based scaffolds for cardiac regeneration after myocardial infarction [J]. Carbohydrate Polym 2023;300:120266. [DOI] [PubMed]
167.Shyu K.G., Wang B.W., Fang W.J., et al. Hyperbaric oxygen-induced long non-coding RNA MALAT1 exosomes suppress MicroRNA-92a expression in a rat model of acute myocardial infarction [J] J Cell Mol Med. 2020;24(22):12945–12954. doi: 10.1111/jcmm.15889. [DOI] [PMC free article] [PubMed] [Google Scholar]
168.Zhang X.J., Liu X., Hu M., et al. Pharmacological inhibition of arachidonate 12-lipoxygenase ameliorates myocardial ischemia-reperfusion injury in multiple species [J] Cell Metab. 2021;33(10):2059. doi: 10.1016/j.cmet.2021.08.014. [DOI] [PubMed] [Google Scholar]
169.Kamarauskaite J., Baniene R., Trumbeckas D., et al. Increased succinate accumulation induces ROS generation in in vivo ischemia/reperfusion-affected rat kidney mitochondria [J] Biomed Res Int. 2020;2020:8855585. doi: 10.1155/2020/8855585. [DOI] [PMC free article] [PubMed] [Google Scholar]
170.Fischer P., Hilfiker-Kleiner D. Survival pathways in hypertrophy and heart failure: the gp130-STAT3 axis [J] Basic Res Cardiol. 2007;102(4):279–297. doi: 10.1007/s00395-007-0658-z. [DOI] [PubMed] [Google Scholar]
171.Katsur M., He Z., Vinokur V., et al. Exosomes from neuronal stem cells may protect the heart from ischaemia/reperfusion injury via JAK1/2 and gp130 [J] J Cell Mol Med. 2021;25(9):4455–4465. doi: 10.1111/jcmm.16515. [DOI] [PMC free article] [PubMed] [Google Scholar]
172.Hu C., Liao J., Huang R., et al. MicroRNA-155-5p in serum derived-exosomes promotes ischaemia-reperfusion injury by reducing CypD ubiquitination by NEDD4 [J] ESC Heart Failure. 2023;10(2):1144–1157. doi: 10.1002/ehf2.14279. [DOI] [PMC free article] [PubMed] [Google Scholar]
173.Bei Y., Lu D., BäR C., et al. miR-486 attenuates cardiac ischemia/reperfusion injury and mediates the beneficial effect of exercise for myocardial protection [J] Mol Therapy: J Am Soc Gene Therapy. 2022;30(4):1675–1691. doi: 10.1016/j.ymthe.2022.01.031. [DOI] [PMC free article] [PubMed] [Google Scholar]
174.Ferreira P., Cravo M., Guerreiro C.S., et al. Fat intake interacts with polymorphisms of Caspase9, FasLigand and PPARgamma apoptotic genes in modulating Crohn's disease activity [J] Clin Nutrit (Edinburgh, Scotland) 2010;29(6):819–823. doi: 10.1016/j.clnu.2010.06.008. [DOI] [PubMed] [Google Scholar]
175.Chambers J.W., Pachori A., Howard S., et al. Inhibition of JNK mitochondrial localization and signaling is protective against ischemia/reperfusion injury in rats [J] J Biol Chem. 2013;288(6):4000–4011. doi: 10.1074/jbc.M112.406777. [DOI] [PMC free article] [PubMed] [Google Scholar]
176.Hou Z., Qin X., Hu Y., et al. Longterm exercise-derived exosomal miR-342-5p: A novel exerkine for cardioprotection [J] Circ Res. 2019;124(9):1386–1400. doi: 10.1161/CIRCRESAHA.118.314635. [DOI] [PubMed] [Google Scholar]
177.Dai Y., Wang S., Chang S., et al. M2 macrophage-derived exosomes carry microRNA-148a to alleviate myocardial ischemia/reperfusion injury via inhibiting TXNIP and the TLR4/NF-κB/NLRP3 inflammasome signaling pathway [J] J Mol Cell Cardiol. 2020;142:65–79. doi: 10.1016/j.yjmcc.2020.02.007. [DOI] [PubMed] [Google Scholar]
178.Zhai T.Y., Cui B.H., Zhou Y., et al. Exosomes released from CaSR-stimulated pmns reduce ischaemia/reperfusion injury [J] Oxid Med Cell Longev. 2021;2021:3010548. doi: 10.1155/2021/3010548. [DOI] [PMC free article] [PubMed] [Google Scholar]
179.Qin S.B., Peng D.Y., Lu J.M., et al. MiR-182-5p inhibited oxidative stress and apoptosis triggered by oxidized low-density lipoprotein via targeting toll-like receptor 4 [J] J Cell Physiol. 2018;233(10):6630–6637. doi: 10.1002/jcp.26389. [DOI] [PubMed] [Google Scholar]
180.Zilun W, Shuaihua Q, Jinxuan Z, et al. Corrigendum to “miRNA-181a over-expression in mesenchymal stem cell-derived exosomes influenced inflammatory response after myocardial ischemia-reperfusion injury. [Life Sci. 232 (2019) 116632] [J]. Life Sci, 2020, 256: 118045. [DOI] [PubMed]
181.Jia C., Chen H., Zhang J., et al. Role of pyroptosis in cardiovascular diseases [J] Int Immunopharmacol. 2019;67:311–318. doi: 10.1016/j.intimp.2018.12.028. [DOI] [PubMed] [Google Scholar]
182.Tang J., Jin L., Liu Y., et al. Exosomes derived from mesenchymal stem cells protect the myocardium against ischemia/reperfusion injury through inhibiting pyroptosis [J] Drug Des Devel Ther. 2020;14:3765–3775. doi: 10.2147/DDDT.S239546. [DOI] [PMC free article] [PubMed] [Google Scholar]
183.Chen G., Wang M., Ruan Z., et al. Mesenchymal stem cell-derived exosomal miR-143-3p suppresses myocardial ischemia-reperfusion injury by regulating autophagy [J] Life Sci. 2021;280 doi: 10.1016/j.lfs.2021.119742. [DOI] [PubMed] [Google Scholar]
184.Li Q., Bu Y., Shao H., et al. Protective effect of bone marrow mesenchymal stem cell-derived exosomes on cardiomyoblast hypoxia-reperfusion injury through the HAND2-AS1/miR-17-5p/Mfn2 axis [J] BMC Cardiovasc Disord. 2023;23(1):114. doi: 10.1186/s12872-023-03148-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
185.Li K.S., Bai Y., Li J., et al. LncRNA HCP5 in hBMSC-derived exosomes alleviates myocardial ischemia reperfusion injury by sponging miR-497 to activate IGF1/PI3K/AKT pathway [J] Int J Cardiol. 2021;342:72–81. doi: 10.1016/j.ijcard.2021.07.042. [DOI] [PubMed] [Google Scholar]
186.Chen G., Yue A., Wang M., et al. The Exosomal lncRNA KLF3-AS1 from ischemic cardiomyocytes mediates IGF-1 secretion by mscs to rescue myocardial ischemia-reperfusion injury [J] Front. Cardiovascular Med. 2021;8 doi: 10.3389/fcvm.2021.671610. [DOI] [PMC free article] [PubMed] [Google Scholar]
187.DéRIJARD B, RAINGEAUD J, BARRETT T, et al. Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms [J]. Science (New York, NY), 1995, 267(5198): 682-5. [DOI] [PubMed]
188.Chen X., Zhu X., Liu Y., et al. Silencing of phospholipase C gamma 2 promotes proliferation of rat hepatocytes in vitro [J] J Cell Biochem. 2018;119(5):4085–4096. doi: 10.1002/jcb.26592. [DOI] [PubMed] [Google Scholar]
189.Wang Y., Shen Y. Exosomal miR-455-3p from BMMSCs prevents cardiac ischemia-reperfusion injury [J] Hum Exp Toxicol. 2022;41 doi: 10.1177/09603271221102508. [DOI] [PubMed] [Google Scholar]
190.Mao S., Zhao J., Zhang Z.J., et al. MiR-183-5p overexpression in bone mesenchymal stem cell-derived exosomes protects against myocardial ischemia/reperfusion injury by targeting FOXO1 [J] Immunobiology. 2022;227(3) doi: 10.1016/j.imbio.2022.152204. [DOI] [PubMed] [Google Scholar]
191.Jeyabal P., Thandavarayan R.A., Joladarashi D., et al. MicroRNA-9 inhibits hyperglycemia-induced pyroptosis in human ventricular cardiomyocytes by targeting ELAVL1 [J] Biochem Biophys Res Commun. 2016;471(4):423–429. doi: 10.1016/j.bbrc.2016.02.065. [DOI] [PMC free article] [PubMed] [Google Scholar]
192.Liu N., Xie L., Xiao P., et al. Cardiac fibroblasts secrete exosome microRNA to suppress cardiomyocyte pyroptosis in myocardial ischemia/reperfusion injury [J] Mol Cell Biochem. 2022;477(4):1249–1260. doi: 10.1007/s11010-021-04343-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
193.Zhao Z.Q., Corvera J.S., Halkos M.E., et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning [J] Am J Physiol Heart Circ Physiol. 2003;285(2):H579–H588. doi: 10.1152/ajpheart.01064.2002. [DOI] [PubMed] [Google Scholar]
194.Luo H., Li X., Li T., et al. microRNA-423-3p exosomes derived from cardiac fibroblasts mediates the cardioprotective effects of ischaemic post-conditioning [J] Cardiovasc Res. 2019;115(7):1189–1204. doi: 10.1093/cvr/cvy231. [DOI] [PubMed] [Google Scholar]
195.L C, Y W, Y P, et al. Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury [J]. Biochemical and biophysical research communications, 2013, 431(3): 566-71. [DOI] [PMC free article] [PubMed]
196.Sun X.H., Wang X., Zhang Y., et al. Exosomes of bone-marrow stromal cells inhibit cardiomyocyte apoptosis under ischemic and hypoxic conditions via miR-486-5p targeting the PTEN/PI3K/AKT signaling pathway [J] Thromb Res. 2019;177:23–32. doi: 10.1016/j.thromres.2019.02.002. [DOI] [PubMed] [Google Scholar]
197.Duran J.M., Makarewich C.A., Sharp T.E., et al. Bone-derived stem cells repair the heart after myocardial infarction through transdifferentiation and paracrine signaling mechanisms [J] Circ Res. 2013;113(5):539–552. doi: 10.1161/CIRCRESAHA.113.301202. [DOI] [PMC free article] [PubMed] [Google Scholar]
198.Schena G.J., Murray E.K., Hildebrand A.N., et al. Cortical bone stem cell-derived exosomes' therapeutic effect on myocardial ischemia-reperfusion and cardiac remodeling [J] Am J Physiol Heart Circ Physiol. 2021;321(6):H1014–H1029. doi: 10.1152/ajpheart.00197.2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
199.Zhang Y., Wei L., Sun D., et al. Tanshinone IIA pretreatment protects myocardium against ischaemia/reperfusion injury through the phosphatidylinositol 3-kinase/Akt-dependent pathway in diabetic rats [J] Diabetes Obes Metab. 2010;12(4):316–322. doi: 10.1111/j.1463-1326.2009.01166.x. [DOI] [PubMed] [Google Scholar]
200.Zhang M.Q., Zheng Y.L., Chen H., et al. Sodium tanshinone IIA sulfonate protects rat myocardium against ischemia-reperfusion injury via activation of PI3K/Akt/FOXO3A/Bim pathway [J] Acta Pharmacol Sin. 2013;34(11):1386–1396. doi: 10.1038/aps.2013.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
201.Fu M., Xie D., Sun Y., et al. Exosomes derived from MSC pre-treated with oridonin alleviates myocardial IR injury by suppressing apoptosis via regulating autophagy activation [J] J Cell Mol Med. 2021;25(12):5486–5496. doi: 10.1111/jcmm.16558. [DOI] [PMC free article] [PubMed] [Google Scholar]
202.Solazzo M., O'Brien F.J., Nicolosi V., et al. The rationale and emergence of electroconductive biomaterial scaffolds in cardiac tissue engineering [J] APL bioengineering. 2019;3(4) doi: 10.1063/1.5116579. [DOI] [PMC free article] [PubMed] [Google Scholar]
203.He X., Wang Q., Zhao Y., et al. Effect of intramyocardial grafting collagen scaffold with mesenchymal stromal cells in patients with chronic ischemic heart disease: a randomized clinical trial [J] JAMA Netw Open. 2020;3(9):e2016236. doi: 10.1001/jamanetworkopen.2020.16236. [DOI] [PMC free article] [PubMed] [Google Scholar]
204.Chen P., Wang L., Fan X., et al. Targeted delivery of extracellular vesicles in heart injury [J] Theranostics. 2021;11(5):2263–2277. doi: 10.7150/thno.51571. [DOI] [PMC free article] [PubMed] [Google Scholar]
205.Zou Y., Li L., Li Y., et al. Restoring cardiac functions after myocardial infarction-ischemia/reperfusion via an exosome anchoring conductive hydrogel [J] ACS Appl Mater Interfaces. 2021;13(48):56892–56908. doi: 10.1021/acsami.1c16481. [DOI] [PubMed] [Google Scholar]
206.Murphy SP, Ibrahim NE, Januzzi JL, JR. Heart failure with reduced ejection fraction: a review [J]. JAMA, 2020;324(5):488-504. [DOI] [PubMed]
207.Roger V.L. Epidemiology of heart failure: a contemporary perspective [J] Circ Res. 2021;128(10):1421–1434. doi: 10.1161/CIRCRESAHA.121.318172. [DOI] [PubMed] [Google Scholar]
208.Xue R., Tan W., Wu Y., et al. Role of exosomal miRNAs in heart failure [J] Front. Cardiovas. Med. 2020;7 doi: 10.3389/fcvm.2020.592412. [DOI] [PMC free article] [PubMed] [Google Scholar]
209.Akhmerov A., Parimon T. Extracellular vesicles, inflammation, and cardiovascular disease [J] Cells. 2022;11(14) doi: 10.3390/cells11142229. [DOI] [PMC free article] [PubMed] [Google Scholar]
210.Hulsmans M., Sager H.B., Roh J.D., et al. Cardiac macrophages promote diastolic dysfunction [J] J Exp Med. 2018;215(2):423–440. doi: 10.1084/jem.20171274. [DOI] [PMC free article] [PubMed] [Google Scholar]
211.Glezeva N., Voon V., Watson C., et al. Exaggerated inflammation and monocytosis associate with diastolic dysfunction in heart failure with preserved ejection fraction: evidence of M2 macrophage activation in disease pathogenesis [J] J Card Fail. 2015;21(2):167–177. doi: 10.1016/j.cardfail.2014.11.004. [DOI] [PubMed] [Google Scholar]
212.Natrus L., Labudzynskyi D., Muzychenko P., et al. Plasma-derived exosomes implement miR-126-associated regulation of cytokines secretion in PBMCs of CHF patients in vitro [J] Acta bio-medica : Atenei Parmensis. 2022;93(3):e2022066. doi: 10.23750/abm.v93i3.12449. [DOI] [PMC free article] [PubMed] [Google Scholar]
213.Díaz HS, Toledo C, Andrade D C, et al. Neuroinflammation in heart failure: new insights for an old disease [J]. J Physiol 2020;598(1):33-59. [DOI] [PubMed]
214.Kaye D.M., Lefkovits J., Jennings G.L., et al. Adverse consequences of high sympathetic nervous activity in the failing human heart [J] J Am Coll Cardiol. 1995;26(5):1257–1263. doi: 10.1016/0735-1097(95)00332-0. [DOI] [PubMed] [Google Scholar]
215.Ma A., Hong J., Shanks J., et al. Upregulating Nrf2 in the RVLM ameliorates sympatho-excitation in mice with chronic heart failure [J] Free Radic Biol Med. 2019;141:84–92. doi: 10.1016/j.freeradbiomed.2019.06.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
216.Tan X., Jiao P.L., Wang Y.K., et al. The phosphoinositide-3 kinase signaling is involved in neuroinflammation in hypertensive rats [J] CNS Neurosci Ther. 2017;23(4):350–359. doi: 10.1111/cns.12679. [DOI] [PMC free article] [PubMed] [Google Scholar]
217.Wu K.L., Chan S.H., Chan J.Y. Neuroinflammation and oxidative stress in rostral ventrolateral medulla contribute to neurogenic hypertension induced by systemic inflammation [J] J Neuroinflammation. 2012;9:212. doi: 10.1186/1742-2094-9-212. [DOI] [PMC free article] [PubMed] [Google Scholar]
218.Saint-Pol J., Gosselet F., Duban-Deweer S., et al. Targeting and crossing the blood-brain barrier with extracellular vesicles [J] Cells. 2020;9(4) doi: 10.3390/cells9040851. [DOI] [PMC free article] [PubMed] [Google Scholar]
219.Xiao Y.C., Wang W., Gao Y., et al. The peripheral circulating exosomal microRNAs Related to central inflammation in chronic heart failure [J] J Cardiovasc Transl Res. 2022;15(3):500–513. doi: 10.1007/s12265-022-10266-5. [DOI] [PubMed] [Google Scholar]
220.Suzuki E., Fujita D., Takahashi M., et al. Therapeutic effects of mesenchymal stem cell-derived exosomes in cardiovascular disease [J] Adv Exp Med Biol. 2017;998:179–185. doi: 10.1007/978-981-10-4397-0_12. [DOI] [PubMed] [Google Scholar]
221.Li Q., Xu Y., Lv K., et al. Small extracellular vesicles containing miR-486-5p promote angiogenesis after myocardial infarction in mice and nonhuman primates [J] Sci Transl Med. 2021;13(584) doi: 10.1126/scitranslmed.abb0202. [DOI] [PubMed] [Google Scholar]
222.Guo Y., Yu Y., Hu S., et al. The therapeutic potential of mesenchymal stem cells for cardiovascular diseases [J] Cell Death Dis. 2020;11(5):349. doi: 10.1038/s41419-020-2542-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
223.Tang J.N., Cores J., Huang K., et al. Concise review: is cardiac cell therapy dead? embarrassing trial outcomes and new directions for the future [J] Stem Cells Transl Med. 2018;7(4):354–359. doi: 10.1002/sctm.17-0196. [DOI] [PMC free article] [PubMed] [Google Scholar]
224.Wang X., Tang Y., Liu Z., et al. The application potential and advance of mesenchymal stem cell-derived exosomes in myocardial infarction [J] Stem Cells Int. 2021;2021:5579904. doi: 10.1155/2021/5579904. [DOI] [PMC free article] [PubMed] [Google Scholar]
225.Nakamura Y., Kita S., Tanaka Y., et al. Adiponectin stimulates exosome release to enhance mesenchymal stem-cell-driven therapy of heart failure in mice [J] Mol Therapy: J Am Soc Gene Therapy. 2020;28(10):2203–2219. doi: 10.1016/j.ymthe.2020.06.026. [DOI] [PMC free article] [PubMed] [Google Scholar]
226.Kita S., Maeda N., Shimomura I. Interorgan communication by exosomes, adipose tissue, and adiponectin in metabolic syndrome [J] J Clin Invest. 2019;129(10):4041–4049. doi: 10.1172/JCI129193. [DOI] [PMC free article] [PubMed] [Google Scholar]
227.AHN S, BASAVANA GOWDA M K, LEE M, et al. Novel linked butanolide dimer compounds increase adiponectin production during adipogenesis in human mesenchymal stem cells through peroxisome proliferator-activated receptor γ modulation [J]. European journal of medicinal chemistry, 2020, 187: 111969. [DOI] [PubMed]
228.Nabeebaccus A., Zheng S., Shah A.M. Heart failure-potential new targets for therapy [J] Br Med Bull. 2016;119(1):99–110. doi: 10.1093/bmb/ldw025. [DOI] [PMC free article] [PubMed] [Google Scholar]
229.Bayoumi A.S., Teoh J.P., Aonuma T., et al. MicroRNA-532 protects the heart in acute myocardial infarction, and represses prss23, a positive regulator of endothelial-to-mesenchymal transition [J] Cardiovasc Res. 2017;113(13):1603–1614. doi: 10.1093/cvr/cvx132. [DOI] [PMC free article] [PubMed] [Google Scholar]
230.Wang Z., Gao D., Wang S., et al. Exosomal microRNA-1246 from human umbilical cord mesenchymal stem cells potentiates myocardial angiogenesis in chronic heart failure [J] Cell Biol Int. 2021;45(11):2211–2225. doi: 10.1002/cbin.11664. [DOI] [PubMed] [Google Scholar]
231.Zhu X., Qiu C., Wang Y., et al. FGFR1 SUMOylation coordinates endothelial angiogenic signaling in angiogenesis [J] PNAS. 2022;119(26) doi: 10.1073/pnas.2202631119. [DOI] [PMC free article] [PubMed] [Google Scholar]
232.Sun P., Zhang K., Hassan S.H., et al. Endothelium-Targeted deletion of microRNA-15a/16-1 promotes poststroke angiogenesis and improves long-term neurological recovery [J] Circ Res. 2020;126(8):1040–1057. doi: 10.1161/CIRCRESAHA.119.315886. [DOI] [PMC free article] [PubMed] [Google Scholar]
233.RäSäNEN M, DEGERMAN J, NISSINEN T A, et al. VEGF-B gene therapy inhibits doxorubicin-induced cardiotoxicity by endothelial protection [J]. Proceedings of the National Academy of Sciences of the United States of America, 2016, 113(46): 13144-9. [DOI] [PMC free article] [PubMed]
234.Tian C., Yang Y., Bai B., et al. Potential of exosomes as diagnostic biomarkers and therapeutic carriers for doxorubicin-induced cardiotoxicity [J] Int J Biol Sci. 2021;17(5):1328–1338. doi: 10.7150/ijbs.58786. [DOI] [PMC free article] [PubMed] [Google Scholar]
235.Ni J., Liu Y., Kang L., et al. Human trophoblast-derived exosomes attenuate doxorubicin-induced cardiac injury by regulating miR-200b and downstream Zeb1 [J] J Nanobiotechnol. 2020;18(1):171. doi: 10.1186/s12951-020-00733-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
236.Ding M., Shi R., Cheng S., et al. Mfn2-mediated mitochondrial fusion alleviates doxorubicin-induced cardiotoxicity with enhancing its anticancer activity through metabolic switch [J] Redox Biol. 2022;52 doi: 10.1016/j.redox.2022.102311. [DOI] [PMC free article] [PubMed] [Google Scholar]
237.Duan J., Liu X., Shen S., et al. Trophoblast Stem-Cell-Derived Exosomes Alleviate Cardiotoxicity of Doxorubicin via Improving Mfn2-Mediated Mitochondrial Fusion [J] Cardiovasc Toxicol. 2023;23(1):23–31. doi: 10.1007/s12012-022-09774-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
238.Pang Y., Ma M., Wang D., et al. Embryonic stem cell-derived exosomes attenuate transverse aortic constriction induced heart failure by increasing angiogenesis [J] Front Cardiovasc Med. 2021;8 doi: 10.3389/fcvm.2021.638771. [DOI] [PMC free article] [PubMed] [Google Scholar]
239.Liu M, López De Juan Abad B, Cheng K. Cardiac fibrosis: Myofibroblast-mediated pathological regulation and drug delivery strategies [J]. Adv Drug Del Rev 2021;173:504-19. [DOI] [PMC free article] [PubMed]
240.Liang T., Gao F., Jiang J., et al. Loss of phosphatase and Tensin homolog promotes cardiomyocyte proliferation and cardiac repair after myocardial infarction [J] Circulation. 2020;142(22):2196–2199. doi: 10.1161/CIRCULATIONAHA.120.046372. [DOI] [PMC free article] [PubMed] [Google Scholar]
241.Hu H.H., Chen D.Q., Wang Y.N., et al. New insights into TGF-β/Smad signaling in tissue fibrosis [J] Chem Biol Interact. 2018;292:76–83. doi: 10.1016/j.cbi.2018.07.008. [DOI] [PubMed] [Google Scholar]
242.Song J., Zhu Y., Li J., et al. Pellino1-mediated TGF-β1 synthesis contributes to mechanical stress induced cardiac fibroblast activation [J] J Mol Cell Cardiol. 2015;79:145–156. doi: 10.1016/j.yjmcc.2014.11.006. [DOI] [PubMed] [Google Scholar]
243.Tang C., Hou Y.X., Shi P.X., et al. Cardiomyocyte-specific Peli1 contributes to the pressure overload-induced cardiac fibrosis through miR-494-3p-dependent exosomal communication [J] FASEB J. 2023;37(1):e22699. doi: 10.1096/fj.202200597R. [DOI] [PubMed] [Google Scholar]
244.Bittle G.J., Morales D., Pietris N., et al. Exosomes isolated from human cardiosphere-derived cells attenuate pressure overload-induced right ventricular dysfunction [J] J Thorac Cardiovasc Surg. 2021;162(3):975. doi: 10.1016/j.jtcvs.2020.06.154. [DOI] [PubMed] [Google Scholar]
245.Jenča D, Melenovský V, Stehlik J, et al. Heart failure after myocardial infarction: incidence and predictors [J]. ESC Heart Failure, 2021; 8(1): 222-37. [DOI] [PMC free article] [PubMed]
246.Yang J., Yang J., Gong X., et al. Recent progress in microneedles-mediated diagnosis, therapy, and theranostic systems [J] Adv Healthc Mater. 2022;11(10):e2102547. doi: 10.1002/adhm.202102547. [DOI] [PubMed] [Google Scholar]
247.Ohayon L., Zhang X., Dutta P. The role of extracellular vesicles in regulating local and systemic inflammation in cardiovascular disease [J] Pharmacol Res. 2021;170 doi: 10.1016/j.phrs.2021.105692. [DOI] [PMC free article] [PubMed] [Google Scholar]
248.Hausenloy D.J., Yellon D.M. Ischaemic conditioning and reperfusion injury [J] Nat Rev Cardiol. 2016;13(4):193–209. doi: 10.1038/nrcardio.2016.5. [DOI] [PubMed] [Google Scholar]
249.Ma L.L., Ding Z.W., Yin P.P., et al. Hypertrophic preconditioning cardioprotection after myocardial ischaemia/reperfusion injury involves ALDH2-dependent metabolism modulation [J] Redox Biol. 2021;43 doi: 10.1016/j.redox.2021.101960. [DOI] [PMC free article] [PubMed] [Google Scholar]
250.Seeger J.P., Benda N.M., Riksen N.P., et al. Heart failure is associated with exaggerated endothelial ischaemia-reperfusion injury and attenuated effect of ischaemic preconditioning [J] Eur J Prev Cardiol. 2016;23(1):33–40. doi: 10.1177/2047487314558377. [DOI] [PubMed] [Google Scholar]
251.Luo Z., Hu X., Wu C., et al. Plasma exosomes generated by ischaemic preconditioning are cardioprotective in a rat heart failure model [J] Br J Anaesth. 2023;130(1):29–38. doi: 10.1016/j.bja.2022.08.040. [DOI] [PMC free article] [PubMed] [Google Scholar]
252.Yong S.B., Song Y., Kim H.J., et al. Mononuclear phagocytes as a target, not a barrier, for drug delivery [J] J Control Release. 2017;259:53–61. doi: 10.1016/j.jconrel.2017.01.024. [DOI] [PubMed] [Google Scholar]
253.Wan Z., Zhao L., Lu F., et al. Mononuclear phagocyte system blockade improves therapeutic exosome delivery to the myocardium [J] Theranostics. 2020;10(1):218–230. doi: 10.7150/thno.38198. [DOI] [PMC free article] [PubMed] [Google Scholar]
254.Zang H., Wu W., Qi L., et al. Autophagy inhibition enables Nrf2 to exaggerate the progression of diabetic cardiomyopathy in mice [J] Diabetes. 2020;69(12):2720–2734. doi: 10.2337/db19-1176. [DOI] [PMC free article] [PubMed] [Google Scholar]
255.Jia G., Demarco V.G., Sowers J.R. Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy [J] Nat Rev Endocrinol. 2016;12(3):144–153. doi: 10.1038/nrendo.2015.216. [DOI] [PMC free article] [PubMed] [Google Scholar]
256.Dewanjee S., Vallamkondu J., Kalra R.S., et al. Autophagy in the diabetic heart: A potential pharmacotherapeutic target in diabetic cardiomyopathy [J] Ageing Res Rev. 2021;68 doi: 10.1016/j.arr.2021.101338. [DOI] [PubMed] [Google Scholar]
257.Tong M., Saito T., Zhai P., et al. Mitophagy is essential for maintaining cardiac function during high fat diet-induced diabetic cardiomyopathy [J] Circ Res. 2019;124(9):1360–1371. doi: 10.1161/CIRCRESAHA.118.314607. [DOI] [PMC free article] [PubMed] [Google Scholar]
258.Yao Q., Ke Z.Q., Guo S., et al. Curcumin protects against diabetic cardiomyopathy by promoting autophagy and alleviating apoptosis [J] J Mol Cell Cardiol. 2018;124:26–34. doi: 10.1016/j.yjmcc.2018.10.004. [DOI] [PubMed] [Google Scholar]
259.Zhu Y., Qian X., Li J., et al. Astragaloside-IV protects H9C2(2–1) cardiomyocytes from high glucose-induced injury via miR-34a-mediated autophagy pathway [J] Artif Cells Nanomed Biotechnol. 2019;47(1):4172–4181. doi: 10.1080/21691401.2019.1687492. [DOI] [PubMed] [Google Scholar]
260.Cui W., Hao Y., Wang M., et al. Inhibition of autophagy facilitates XY03-EA-mediated neuroprotection against the cerebral ischemia/reperfusion injury in rats [J] Oxid Med Cell Longev. 2022;2022:7013299. doi: 10.1155/2022/7013299. [DOI] [PMC free article] [PubMed] [Google Scholar]
261.Richter K., Haslbeck M., Buchner J. The heat shock response: life on the verge of death [J] Mol Cell. 2010;40(2):253–266. doi: 10.1016/j.molcel.2010.10.006. [DOI] [PubMed] [Google Scholar]
262.Wang X., Gu H., Huang W., et al. Hsp20-mediated activation of exosome biogenesis in cardiomyocytes improves cardiac function and angiogenesis in diabetic mice [J] Diabetes. 2016;65(10):3111–3128. doi: 10.2337/db15-1563. [DOI] [PMC free article] [PubMed] [Google Scholar]
263.Pattingre S., Tassa A., Qu X., et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy [J] Cell. 2005;122(6):927–939. doi: 10.1016/j.cell.2005.07.002. [DOI] [PubMed] [Google Scholar]
264.Liang X.H., Jackson S., Seaman M., et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1 [J] Nature. 1999;402(6762):672–676. doi: 10.1038/45257. [DOI] [PubMed] [Google Scholar]
265.Levine B., Sinha S., Kroemer G. Bcl-2 family members: dual regulators of apoptosis and autophagy [J] Autophagy. 2008;4(5):600–606. doi: 10.4161/auto.6260. [DOI] [PMC free article] [PubMed] [Google Scholar]
266.He C., Zhu H., Li H., et al. Dissociation of Bcl-2-Beclin1 complex by activated AMPK enhances cardiac autophagy and protects against cardiomyocyte apoptosis in diabetes [J] Diabetes. 2013;62(4):1270–1281. doi: 10.2337/db12-0533. [DOI] [PMC free article] [PubMed] [Google Scholar]
267.Hu J., Wang S., Xiong Z., et al. Exosomal Mst1 transfer from cardiac microvascular endothelial cells to cardiomyocytes deteriorates diabetic cardiomyopathy [J] Biochim Biophys Acta. 2018;1864(11):3639–3649. doi: 10.1016/j.bbadis.2018.08.026. [DOI] [PubMed] [Google Scholar]
268.Krishnamurthy P., Rajasingh J., Lambers E., et al. IL-10 inhibits inflammation and attenuates left ventricular remodeling after myocardial infarction via activation of STAT3 and suppression of HuR [J] Circ Res. 2009;104(2):e9–e. doi: 10.1161/CIRCRESAHA.108.188243. [DOI] [PMC free article] [PubMed] [Google Scholar]
269.Govindappa P.K., Patil M., Garikipati V.N.S., et al. Targeting exosome-associated human antigen R attenuates fibrosis and inflammation in diabetic heart [J] FASEB J. 2020;34(2):2238–2251. doi: 10.1096/fj.201901995R. [DOI] [PMC free article] [PubMed] [Google Scholar]
270.Wei B., Lu F., Kong Q., et al. Trehalose induces B cell autophagy to alleviate myocardial injury via the AMPK/ULK1 signalling pathway in acute viral myocarditis induced by Coxsackie virus B3 [J] Int J Biochem Cell Biol. 2022;146 doi: 10.1016/j.biocel.2022.106208. [DOI] [PubMed] [Google Scholar]
271.Zhang Z., Chen L., Chen X., et al. Exosomes derived from human umbilical cord mesenchymal stem cells (HUCMSC-EXO) regulate autophagy through AMPK-ULK1 signaling pathway to ameliorate diabetic cardiomyopathy [J] Biochem Biophys Res Commun. 2022;632:195–203. doi: 10.1016/j.bbrc.2022.10.001. [DOI] [PubMed] [Google Scholar]
272.Xiong J., Hu H., Guo R., et al. Mesenchymal stem cell exosomes as a new strategy for the treatment of diabetes complications [J] Front Endocrinol. 2021;12 doi: 10.3389/fendo.2021.646233. [DOI] [PMC free article] [PubMed] [Google Scholar]
273.Lee J.Y., Chung J., Byun Y., et al. Mesenchymal stem cell-derived small extracellular vesicles protect cardiomyocytes from doxorubicin-induced cardiomyopathy by upregulating survivin expression via the miR-199a-3p-Akt-Sp1/p53 signaling pathway [J] Int J Mol Sci. 2021;22(13) doi: 10.3390/ijms22137102. [DOI] [PMC free article] [PubMed] [Google Scholar]
274.Milano G., Biemmi V., Lazzarini E., et al. Intravenous administration of cardiac progenitor cell-derived exosomes protects against doxorubicin/trastuzumab-induced cardiac toxicity [J] Cardiovasc Res. 2020;116(2):383–392. doi: 10.1093/cvr/cvz108. [DOI] [PubMed] [Google Scholar]
275.Pollack A., Kontorovich A.R., Fuster V., et al. Viral myocarditis–diagnosis, treatment options, and current controversies [J] Nat Rev Cardiol. 2015;12(11):670–680. doi: 10.1038/nrcardio.2015.108. [DOI] [PubMed] [Google Scholar]
276.Caforio A.L., Pankuweit S., Arbustini E., et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases [J] Eur Heart J. 2013;34(33) doi: 10.1093/eurheartj/eht210. [DOI] [PubMed] [Google Scholar]
277.Zhao H., Shang Q., Pan Z., et al. Exosomes from adipose-derived stem cells attenuate adipose inflammation and obesity through polarizing M2 macrophages and beiging in white adipose tissue [J] Diabetes. 2018;67(2):235–247. doi: 10.2337/db17-0356. [DOI] [PubMed] [Google Scholar]
278.Gu X., Li Y., Chen K., et al. Exosomes derived from umbilical cord mesenchymal stem cells alleviate viral myocarditis through activating AMPK/mTOR-mediated autophagy flux pathway [J] J Cell Mol Med. 2020;24(13):7515–7530. doi: 10.1111/jcmm.15378. [DOI] [PMC free article] [PubMed] [Google Scholar]
279.Sun P., Wang N., Zhao P., et al. Circulating exosomes control CD4(+) T cell immunometabolic functions via the transfer of miR-142 as a novel mediator in myocarditis [J] Mol Therapy: J Am Soc Gene Therapy. 2020;28(12):2605–2620. doi: 10.1016/j.ymthe.2020.08.015. [DOI] [PMC free article] [PubMed] [Google Scholar]
280.Wang Y, Jin P, Liu J, et al. Exosomal microRNA-122 mediates obesity-related cardiomyopathy through suppressing mitochondrial ADP-ribosylation factor-like 2 [J]. Clinical science (London, England: 1979), 2019, 133(17): 1871-81. [DOI] [PubMed]
281.Gartz M., Lin C.W., Sussman M.A., et al. Duchenne muscular dystrophy (DMD) cardiomyocyte-secreted exosomes promote the pathogenesis of DMD-associated cardiomyopathy [J] Dis Model Mech. 2020;13(11) doi: 10.1242/dmm.045559. [DOI] [PMC free article] [PubMed] [Google Scholar]
282.Li F., Zhang K., Xu T., et al. Exosomal microRNA-29a mediates cardiac dysfunction and mitochondrial inactivity in obesity-related cardiomyopathy [J] Endocrine. 2019;63(3):480–488. doi: 10.1007/s12020-018-1753-7. [DOI] [PubMed] [Google Scholar]
283.Vandergriff A., Huang K., Shen D., et al. Targeting regenerative exosomes to myocardial infarction using cardiac homing peptide [J] Theranostics. 2018;8(7):1869–1878. doi: 10.7150/thno.20524. [DOI] [PMC free article] [PubMed] [Google Scholar]
284.Luan X., Sansanaphongpricha K., Myers I., et al. Engineering exosomes as refined biological nanoplatforms for drug delivery [J] Acta Pharmacol Sin. 2017;38(6):754–763. doi: 10.1038/aps.2017.12. [DOI] [PMC free article] [PubMed] [Google Scholar]
285.Huang K., Ozpinar E.W., Su T., et al. An off-the-shelf artificial cardiac patch improves cardiac repair after myocardial infarction in rats and pigs [J] Sci Transl Med. 2020;12(538) doi: 10.1126/scitranslmed.aat9683. [DOI] [PMC free article] [PubMed] [Google Scholar]
286.Tang J., Wang J., Huang K., et al. Cardiac cell-integrated microneedle patch for treating myocardial infarction [J] Sci Adv. 2018;4(11):eaat9365. doi: 10.1126/sciadv.aat9365. [DOI] [PMC free article] [PubMed] [Google Scholar]
287.Cannata A., Petrella D., Russo C.F., et al. Postsurgical intrapericardial adhesions: mechanisms of formation and prevention [J] Ann Thorac Surg. 2013;95(5):1818–1826. doi: 10.1016/j.athoracsur.2012.11.020. [DOI] [PubMed] [Google Scholar]
288.Cheng G., Zhu D., Huang K., et al. Minimally invasive delivery of a hydrogel-based exosome patch to prevent heart failure [J] J Mol Cell Cardiol. 2022;169:113–121. doi: 10.1016/j.yjmcc.2022.04.020. [DOI] [PubMed] [Google Scholar]
289.Huang J.P., Chang C.C., Kuo C.Y., et al. Exosomal microRNAs miR-30d-5p and miR-126a-5p are associated with heart failure with preserved ejection fraction in STZ-induced type 1 diabetic rats [J] Int J Mol Sci. 2022;23(14) doi: 10.3390/ijms23147514. [DOI] [PMC free article] [PubMed] [Google Scholar]
290.Kang J.Y., Mun D., Kim H., et al. Serum exosomal long noncoding RNAs as a diagnostic biomarker for atrial fibrillation [J] Heart Rhythm. 2022;19(9):1450–1458. doi: 10.1016/j.hrthm.2022.05.033. [DOI] [PubMed] [Google Scholar]
291.Wang Y., Liang J., Xu J., et al. Circulating exosomes and exosomal lncRNA HIF1A-AS1 in atherosclerosis [J] Int J Clin Exp Path. 2017;10(8):8383–8388. [PMC free article] [PubMed] [Google Scholar]
292.Liang C., Zhang L., Lian X., et al. Circulating exosomal SOCS2-AS1 acts as a novel biomarker in predicting the diagnosis of coronary artery disease [J] Biomed Res Int. 2020;2020:9182091. doi: 10.1155/2020/9182091. [DOI] [PMC free article] [PubMed] [Google Scholar]
293.Zheng M.L., Liu X.Y., Han R.J., et al. Circulating exosomal long non-coding RNAs in patients with acute myocardial infarction [J] J Cell Mol Med. 2020;24(16):9388–9396. doi: 10.1111/jcmm.15589. [DOI] [PMC free article] [PubMed] [Google Scholar]
294.Bai C., Liu Y., Zhao Y., et al. Circulating exosome-derived miR-122-5p is a novel biomarker for prediction of postoperative atrial fibrillation [J] J Cardiovasc Transl Res. 2022;15(6):1393–1405. doi: 10.1007/s12265-022-10267-4. [DOI] [PubMed] [Google Scholar]
295.Chang S.N., Chen J.J., Wu J.H., et al. Association between exosomal miRNAs and coronary artery disease by next-generation sequencing [J] Cells. 2021;11(1) doi: 10.3390/cells11010098. [DOI] [PMC free article] [PubMed] [Google Scholar]
296.Zhang P., Liang T., Chen Y., et al. Circulating exosomal miRNAs as novel biomarkers for stable coronary artery disease [J] Biomed Res Int. 2020;2020:3593962. doi: 10.1155/2020/3593962. [DOI] [PMC free article] [PubMed] [Google Scholar]
297.Wu W.P., Pan Y.H., Cai M.Y., et al. Plasma-derived exosomal circular RNA hsa_circ_0005540 as a novel diagnostic biomarker for coronary artery disease [J] Dis Markers. 2020;2020:3178642. doi: 10.1155/2020/3178642. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0005] 1.YáñEZ-Mó M, Siljander PR, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions [J]. J. Extracell. Vesicles, 2015, 4: 27066. [DOI] [PMC free article] [PubMed]

[b0010] 2.Wang C., Li Z., Liu Y., et al. Exosomes in atherosclerosis: performers, bystanders, biomarkers, and therapeutic targets [J] Theranostics. 2021;11(8):3996–4010. doi: 10.7150/thno.56035. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0015] 3.Kalluri R, Lebleu V S. The biology, function, and biomedical applications of exosomes [J]. Science (New York, NY), 2020, 367(6478). [DOI] [PMC free article] [PubMed]

[b0020] 4.Kalluri R. The biology and function of exosomes in cancer [J] J Clin Invest. 2016;126(4):1208–1215. doi: 10.1172/JCI81135. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0025] 5.Wen S.W., Lima L.G., Lobb R.J., et al. Breast cancer-derived exosomes reflect the cell-of-origin phenotype [J] Proteomics. 2019;19(8):e1800180. doi: 10.1002/pmic.201800180. [DOI] [PubMed] [Google Scholar]

[b0030] 6.Han L., Lam E.W., Sun Y. Extracellular vesicles in the tumor microenvironment: old stories, but new tales [J] Mol Can. 2019;18(1):59. doi: 10.1186/s12943-019-0980-8. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0035] 7.Lao K.H., Zeng L., Xu Q. Endothelial and smooth muscle cell transformation in atherosclerosis [J] Curr Opin Lipidol. 2015;26(5):449–456. doi: 10.1097/MOL.0000000000000219. [DOI] [PubMed] [Google Scholar]

[b0040] 8.Liu Q., Piao H., Wang Y., et al. Circulating exosomes in cardiovascular disease: Novel carriers of biological information [J] Biomed pharmacotherapy = Biomed pharmacotherapie. 2021;135 doi: 10.1016/j.biopha.2020.111148. [DOI] [PubMed] [Google Scholar]

[b0045] 9.Zhao D., Liu J., Wang M., et al. Epidemiology of cardiovascular disease in China: current features and implications [J] Nat Rev Cardiol. 2019;16(4):203–212. doi: 10.1038/s41569-018-0119-4. [DOI] [PubMed] [Google Scholar]

[b0050] 10.van Niel G., D'Angelo G., Raposo G. Shedding light on the cell biology of extracellular vesicles [J] Nat Rev Mol Cell Biol. 2018;19(4):213–228. doi: 10.1038/nrm.2017.125. [DOI] [PubMed] [Google Scholar]

[b0055] 11.Lai JJ, Chau ZL, Chen SY, et al. Exosome processing and characterization approaches for research and technology development [J]. Adv Sci (Weinheim, Baden-Wurttemberg, Germany), 2022, 9(15): e2103222. [DOI] [PMC free article] [PubMed]

[b0060] 12.Anakor E., le Gall L., Dumonceaux J., et al. Exosomes in ageing and motor neurone disease: biogenesis, uptake mechanisms, modifications in disease and uses in the development of biomarkers and therapeutics [J] Cells. 2021;10(11) doi: 10.3390/cells10112930. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0065] 13.Kamerkar S., Lebleu V.S., Sugimoto H., et al. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer [J] Nature. 2017;546(7659):498–503. doi: 10.1038/nature22341. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0070] 14.Hanayama R., Tanaka M., Miwa K., et al. Identification of a factor that links apoptotic cells to phagocytes [J] Nature. 2002;417(6885):182–187. doi: 10.1038/417182a. [DOI] [PubMed] [Google Scholar]

[b0075] 15.Saunderson S.C., Dunn A.C., Crocker P.R., et al. CD169 mediates the capture of exosomes in spleen and lymph node [J] Blood. 2014;123(2):208–216. doi: 10.1182/blood-2013-03-489732. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0080] 16.Segura E., Nicco C., Lombard B., et al. ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming [J] Blood. 2005;106(1):216–223. doi: 10.1182/blood-2005-01-0220. [DOI] [PubMed] [Google Scholar]

[b0085] 17.Nolte-'T Hoen E N, Buschow S I, Anderton S M, et al. Activated T cells recruit exosomes secreted by dendritic cells via LFA-1 [J]. Blood, 2009;113(9):1977–81. [DOI] [PubMed]

[b0090] 18.Hakulinen J., Junnikkala S., Sorsa T., et al. Complement inhibitor membrane cofactor protein (MCP; CD46) is constitutively shed from cancer cell membranes in vesicles and converted by a metalloproteinase to a functionally active soluble form [J] Eur J Immunol. 2004;34(9):2620–2629. doi: 10.1002/eji.200424969. [DOI] [PubMed] [Google Scholar]

[b0095] 19.Tian T., Zhu Y.L., Zhou Y.Y., et al. Exosome uptake through clathrin-mediated endocytosis and macropinocytosis and mediating miR-21 delivery [J] J Biol Chem. 2014;289(32):22258–22267. doi: 10.1074/jbc.M114.588046. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0100] 20.Parton R.G., Tillu V.A., Collins B.M. Caveolae [J] Curr Biol. 2018;28(8):R402–R405. doi: 10.1016/j.cub.2017.11.075. [DOI] [PubMed] [Google Scholar]

[b0105] 21.El-Sayed A., Harashima H. Endocytosis of gene delivery vectors: from clathrin-dependent to lipid raft-mediated endocytosis [J] Mol Therapy: J. Am Soc Gene Therapy. 2013;21(6):1118–1130. doi: 10.1038/mt.2013.54. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0110] 22.Andreu Z., YáñEZ-Mó M. Tetraspanins in extracellular vesicle formation and function [J] Front Immunol. 2014;5:442. doi: 10.3389/fimmu.2014.00442. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0115] 23.Gao L., Qiu F., Cao H., et al. Therapeutic delivery of microRNA-125a-5p oligonucleotides improves recovery from myocardial ischemia/reperfusion injury in mice and swine [J] Theranostics. 2023;13(2):685–703. doi: 10.7150/thno.73568. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0120] 24.Raposo G., Nijman H.W., Stoorvogel W., et al. B lymphocytes secrete antigen-presenting vesicles [J] J Exp Med. 1996;183(3):1161–1172. doi: 10.1084/jem.183.3.1161. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0125] 25.Tabas I., Bornfeldt K.E. Macrophage phenotype and function in different stages of atherosclerosis [J] Circ Res. 2016;118(4):653–667. doi: 10.1161/CIRCRESAHA.115.306256. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0130] 26.Libby P., Loscalzo J., Ridker P.M., et al. Inflammation, immunity, and infection in atherothrombosis: JACC review topic of the week [J] J Am Coll Cardiol. 2018;72(17):2071–2081. doi: 10.1016/j.jacc.2018.08.1043. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0135] 27.Libby P. Inflammation in atherosclerosis-no longer a theory [J] Clin Chem. 2021;67(1):131–142. doi: 10.1093/clinchem/hvaa275. [DOI] [PubMed] [Google Scholar]

[b0140] 28.Libby P. The changing landscape of atherosclerosis [J] Nature. 2021;592(7855):524–533. doi: 10.1038/s41586-021-03392-8. [DOI] [PubMed] [Google Scholar]

[b0145] 29.Dzau V.J., Braun-Dullaeus R.C., Sedding D.G. Vascular proliferation and atherosclerosis: new perspectives and therapeutic strategies [J] Nat Med. 2002;8(11):1249–1256. doi: 10.1038/nm1102-1249. [DOI] [PubMed] [Google Scholar]

[b0150] 30.Libby P., Ridker P.M., Hansson G.K. Progress and challenges in translating the biology of atherosclerosis [J] Nature. 2011;473(7347):317–325. doi: 10.1038/nature10146. [DOI] [PubMed] [Google Scholar]

[b0155] 31.Davis G.E., Senger D.R. Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization [J] Circ Res. 2005;97(11):1093–1107. doi: 10.1161/01.RES.0000191547.64391.e3. [DOI] [PubMed] [Google Scholar]

[b0160] 32.Baruah J., Wary K.K. Exosomes in the regulation of vascular endothelial cell regeneration [J] Front Cell Dev Biol. 2019;7:353. doi: 10.3389/fcell.2019.00353. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0165] 33.Chen Y.T., Yuan H.X., Ou Z.J., et al. Microparticles (Exosomes) and atherosclerosis [J] Curr Atheroscler Rep. 2020;22(6):23. doi: 10.1007/s11883-020-00841-z. [DOI] [PubMed] [Google Scholar]

[b0170] 34.Heo J, Kang H. Exosome-Based Treatment for Atherosclerosis [J]. International journal of molecular sciences 2022;23(2). [DOI] [PMC free article] [PubMed]

[b0175] 35.Leroyer A.S., Isobe H., LESèCHE G., et al. Cellular origins and thrombogenic activity of microparticles isolated from human atherosclerotic plaques [J] J Am Coll Cardiol. 2007;49(7):772–777. doi: 10.1016/j.jacc.2006.10.053. [DOI] [PubMed] [Google Scholar]

[b0180] 36.Mallat Z., Hugel B., Ohan J., et al. Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity [J] Circulation. 1999;99(3):348–353. doi: 10.1161/01.cir.99.3.348. [DOI] [PubMed] [Google Scholar]

[b0185] 37.Tong X., Dang X., Liu D., et al. Exosome-derived circ_0001785 delays atherogenesis through the ceRNA network mechanism of miR-513a-5p/TGFBR3 [J] J Nanobiotechnol. 2023;21(1):362. doi: 10.1186/s12951-023-02076-x. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0190] 38.Ding Z., Pothineni N.V.K., Goel A., et al. PCSK9 and inflammation: role of shear stress, pro-inflammatory cytokines, and LOX-1 [J] Cardiovasc Res. 2020;116(5):908–915. doi: 10.1093/cvr/cvz313. [DOI] [PubMed] [Google Scholar]

[b0195] 39.Ding J., Li H., Liu W., et al. miR-186-5p dysregulation in serum exosomes from patients with AMI aggravates atherosclerosis via targeting LOX-1 [J] Int J Nanomed. 2022;17:6301–6316. doi: 10.2147/IJN.S383904. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0200] 40.Hayden M.S., Ghosh S. Shared principles in NF-kappaB signaling [J] Cell. 2008;132(3):344–362. doi: 10.1016/j.cell.2008.01.020. [DOI] [PubMed] [Google Scholar]

[b0205] 41.Gilmore T.D. Introduction to NF-kappaB: players, pathways, perspectives [J] Oncogene. 2006;25(51):6680–6684. doi: 10.1038/sj.onc.1209954. [DOI] [PubMed] [Google Scholar]

[b0210] 42.Brasier A.R. The NF-kappaB regulatory network [J] Cardiovasc Toxicol. 2006;6(2):111–130. doi: 10.1385/ct:6:2:111. [DOI] [PubMed] [Google Scholar]

[b0215] 43.Perkins N.D. Integrating cell-signalling pathways with NF-kappaB and IKK function [J] Nat Rev Mol Cell Biol. 2007;8(1):49–62. doi: 10.1038/nrm2083. [DOI] [PubMed] [Google Scholar]

[b0220] 44.Zhu Z., Zhang G., Li D., et al. Silencing of specificity protein 1 protects H9c2 cells against lipopolysaccharide-induced injury via binding to the promoter of chemokine CXC receptor 4 and suppressing NF-κB signaling [J] Bioengineered. 2022;13(2):3395–3409. doi: 10.1080/21655979.2022.2026548. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0225] 45.Chan J., Prado-Lourenco L., Khachigian L.M., et al. TRAIL promotes VSMC proliferation and neointima formation in a FGF-2-, Sp1 phosphorylation-, and NFkappaB-dependent manner [J] Circ Res. 2010;106(6):1061–1071. doi: 10.1161/CIRCRESAHA.109.206029. [DOI] [PubMed] [Google Scholar]

[b0230] 46.Zheng B., Yin W.N., Suzuki T., et al. Exosome-mediated miR-155 transfer from smooth muscle cells to endothelial cells induces endothelial injury and promotes atherosclerosis [J] Mol Therapy: J Am Soc Gene Therapy. 2017;25(6):1279–1294. doi: 10.1016/j.ymthe.2017.03.031. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]

[b0235] 47.Liu P., Wang S., Wang G., et al. Macrophage-derived exosomal miR-4532 promotes endothelial cells injury by targeting SP1 and NF-κB P65 signalling activation [J] J Cell Mol Med. 2022;26(20):5165–5180. doi: 10.1111/jcmm.17541. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0240] 48.DéLéRIS P, Bacqueville D, Gayral S, et al. SHIP-2 and PTEN are expressed and active in vascular smooth muscle cell nuclei, but only SHIP-2 is associated with nuclear speckles [J]. J Biol Chem 2003;278(40):38884-91. [DOI] [PubMed]

[b0245] 49.Pi S., Mao L., Chen J., et al. The P2RY12 receptor promotes VSMC-derived foam cell formation by inhibiting autophagy in advanced atherosclerosis [J] Autophagy. 2021;17(4):980–1000. doi: 10.1080/15548627.2020.1741202. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0250] 50.Sasaoka T., Kikuchi K., Wada T., et al. Dual role of SRC homology domain 2-containing inositol phosphatase 2 in the regulation of platelet-derived growth factor and insulin-like growth factor I signaling in rat vascular smooth muscle cells [J] Endocrinology. 2003;144(9):4204–4214. doi: 10.1210/en.2003-0190. [DOI] [PubMed] [Google Scholar]

[b0255] 51.Ren L., Chen S., Yao D., et al. OxLDL-stimulated macrophage exosomes promote proatherogenic vascular smooth muscle cell viability and invasion via delivering miR-186-5p then inactivating SHIP2 mediated PI3K/AKT/mTOR pathway [J] Mol Immunol. 2022;146:27–37. doi: 10.1016/j.molimm.2022.02.018. [DOI] [PubMed] [Google Scholar]

[b0260] 52.Babic M., Schuchardt M., TöLLE M., et al. In times of tobacco-free nicotine consumption: the influence of nicotine on vascular calcification [J] Eur J Clin Invest. 2019;49(4):e13077. doi: 10.1111/eci.13077. [DOI] [PubMed] [Google Scholar]

[b0265] 53.Wang Z., Liu B., Zhu J., et al. Nicotine-mediated autophagy of vascular smooth muscle cell accelerates atherosclerosis via nAChRs/ROS/NF-κB signaling pathway [J] Atherosclerosis. 2019;284:1–10. doi: 10.1016/j.atherosclerosis.2019.02.008. [DOI] [PubMed] [Google Scholar]

[b0270] 54.Moulton K.S., Li M., Strand K., et al. PTEN deficiency promotes pathological vascular remodeling of human coronary arteries [J] JCI insight. 2018;3(4) doi: 10.1172/jci.insight.97228. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0275] 55.Furgeson S.B., Simpson P.A., Park I., et al. Inactivation of the tumour suppressor, PTEN, in smooth muscle promotes a pro-inflammatory phenotype and enhances neointima formation [J] Cardiovasc Res. 2010;86(2):274–282. doi: 10.1093/cvr/cvp425. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0280] 56.Zhu J., Liu B., Wang Z., et al. Exosomes from nicotine-stimulated macrophages accelerate atherosclerosis through miR-21-3p/PTEN-mediated VSMC migration and proliferation [J] Theranostics. 2019;9(23):6901–6919. doi: 10.7150/thno.37357. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0285] 57.Bouchareychas L., Duong P., Covarrubias S., et al. Macrophage exosomes resolve atherosclerosis by regulating hematopoiesis and inflammation via MicroRNA Cargo [J] Cell Rep. 2020;32(2) doi: 10.1016/j.celrep.2020.107881. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0290] 58.Zhang S., Wang W., Wu X., et al. Regulatory roles of circular RNAs in coronary artery disease [J] Mol. Therapy Nucleic Acids. 2020;21:172–179. doi: 10.1016/j.omtn.2020.05.024. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0295] 59.Tong K.L., Tan K.E., Lim Y.Y., et al. CircRNA-miRNA interactions in atherogenesis [J] Mol Cell Biochem. 2022;477(12):2703–2733. doi: 10.1007/s11010-022-04455-8. [DOI] [PubMed] [Google Scholar]

[b0300] 60.Xiong F., Mao R., Zhang L., et al. CircNPHP4 in monocyte-derived small extracellular vesicles controls heterogeneous adhesion in coronary heart atherosclerotic disease [J] Cell Death Dis. 2021;12(10):948. doi: 10.1038/s41419-021-04253-y. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0305] 61.Gao W., Liu H., Yuan J., et al. Exosomes derived from mature dendritic cells increase endothelial inflammation and atherosclerosis via membrane TNF-α mediated NF-κB pathway [J] J Cell Mol Med. 2016;20(12):2318–2327. doi: 10.1111/jcmm.12923. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0310] 62.Lin B., Xie W., Zeng C., et al. Transfer of exosomal microRNA-203-3p from dendritic cells to bone marrow-derived macrophages reduces development of atherosclerosis by downregulating Ctss in mice [J] Aging. 2021;13(11):15638–15658. doi: 10.18632/aging.103842. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0315] 63.Li J., Xue H., Li T., et al. Exosomes derived from mesenchymal stem cells attenuate the progression of atherosclerosis in ApoE(-/-) mice via miR-let7 mediated infiltration and polarization of M2 macrophage [J] Biochem Biophys Res Commun. 2019;510(4):565–572. doi: 10.1016/j.bbrc.2019.02.005. [DOI] [PubMed] [Google Scholar]

[b0320] 64.Ma J., Chen L., Zhu X., et al. Mesenchymal stem cell-derived exosomal miR-21a-5p promotes M2 macrophage polarization and reduces macrophage infiltration to attenuate atherosclerosis [J] Acta Biochim Biophy Sin. 2021;53(9):1227–1236. doi: 10.1093/abbs/gmab102. [DOI] [PubMed] [Google Scholar]

[b0325] 65.Xing X., Li Z., Yang X., et al. Adipose-derived mesenchymal stem cells-derived exosome-mediated microRNA-342-5p protects endothelial cells against atherosclerosis [J] Aging. 2020;12(4):3880–3898. doi: 10.18632/aging.102857. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0330] 66.Sun L., He X., Zhang T., et al. Knockdown of mesenchymal stem cell-derived exosomal LOC100129516 suppresses the symptoms of atherosclerosis via upregulation of the PPARγ/LXRα/ABCA1 signaling pathway [J] Int J Mol Med. 2021;48(6) doi: 10.3892/ijmm.2021.5041. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0335] 67.Silva-GARCÍA O, Valdez-Alarcón JJ, Baizabal-Aguirre VM. The Wnt/β-catenin signaling pathway controls the inflammatory response in infections caused by pathogenic bacteria [J]. Mediat Inflam 2014: 310183. [DOI] [PMC free article] [PubMed]

[b0340] 68.Gustafson B., Smith U. Cytokines promote Wnt signaling and inflammation and impair the normal differentiation and lipid accumulation in 3T3-L1 preadipocytes [J] J Biol Chem. 2006;281(14):9507–9516. doi: 10.1074/jbc.M512077200. [DOI] [PubMed] [Google Scholar]

[b0345] 69.Gao H., Yu Z., Li Y., et al. miR-100-5p in human umbilical cord mesenchymal stem cell-derived exosomes mediates eosinophilic inflammation to alleviate atherosclerosis via the FZD5/Wnt/β-catenin pathway [J] Acta Biochim Biophy Sin. 2021;53(9):1166–1176. doi: 10.1093/abbs/gmab093. [DOI] [PubMed] [Google Scholar]

[b0350] 70.Döring Y, Soehnlein O, Weber C. Neutrophil extracellular traps in atherosclerosis and atherothrombosis [J]. Circulat Res 2017;120(4):736-43. [DOI] [PubMed]

[b0355] 71.Chen L., Hu L., Li Q., et al. Exosome-encapsulated miR-505 from ox-LDL-treated vascular endothelial cells aggravates atherosclerosis by inducing NET formation [J] Acta Biochim Biophy Sin. 2019;51(12):1233–1241. doi: 10.1093/abbs/gmz123. [DOI] [PubMed] [Google Scholar]

[b0360] 72.Gao H., Wang X., Lin C., et al. Exosomal MALAT1 derived from ox-LDL-treated endothelial cells induce neutrophil extracellular traps to aggravate atherosclerosis [J] Biol Chem. 2020;401(3):367–376. doi: 10.1515/hsz-2019-0219. [DOI] [PubMed] [Google Scholar]

[b0365] 73.Zhang Y.G., Song Y., Guo X.L., et al. Exosomes derived from oxLDL-stimulated macrophages induce neutrophil extracellular traps to drive atherosclerosis [J] Cell cycle (Georgetown, Tex) 2019;18(20):2674–2684. doi: 10.1080/15384101.2019.1654797. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0370] 74.Galluzzi L., Green D.R. Autophagy-independent functions of the autophagy machinery [J] Cell. 2019;177(7):1682–1699. doi: 10.1016/j.cell.2019.05.026. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0375] 75.Guo F.X., Wu Q., Li P., et al. The role of the LncRNA-FA2H-2-MLKL pathway in atherosclerosis by regulation of autophagy flux and inflammation through mTOR-dependent signaling [J] Cell Death Differ. 2019;26(9):1670–1687. doi: 10.1038/s41418-018-0235-z. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0380] 76.Ke X., Liao Z., Luo X., et al. Endothelial colony-forming cell-derived exosomal miR-21-5p regulates autophagic flux to promote vascular endothelial repair by inhibiting SIPL1A2 in atherosclerosis [J] Cell Commun Signal. 2022;20(1):30. doi: 10.1186/s12964-022-00828-0. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0385] 77.van Gaal L.F., Mertens I.L., de Block C.E. Mechanisms linking obesity with cardiovascular disease [J] Nature. 2006;444(7121):875–880. doi: 10.1038/nature05487. [DOI] [PubMed] [Google Scholar]

[b0390] 78.Flaherty SE, 3RD, Grijalva A, Xu X, et al. A lipase-independent pathway of lipid release and immune modulation by adipocytes [J]. Science (New York, NY), 2019, 363(6430): 989-93. [DOI] [PMC free article] [PubMed]

[b0395] 79.Xie Z., Wang X., Liu X., et al. Adipose-derived exosomes exert proatherogenic effects by regulating macrophage foam cell formation and polarization [J] J Am Heart Assoc. 2018;7(5) doi: 10.1161/JAHA.117.007442. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0400] 80.Pan Y., Hui X., Hoo R.L.C., et al. Adipocyte-secreted exosomal microRNA-34a inhibits M2 macrophage polarization to promote obesity-induced adipose inflammation [J] J Clin Invest. 2019;129(2):834–849. doi: 10.1172/JCI123069. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0405] 81.Tang Y., Yang L.J., Liu H., et al. Exosomal miR-27b-3p secreted by visceral adipocytes contributes to endothelial inflammation and atherogenesis [J] Cell Rep. 2023;42(1) doi: 10.1016/j.celrep.2022.111948. [DOI] [PubMed] [Google Scholar]

[b0410] 82.Song Y., Li H., Ren X., et al. SNHG9, delivered by adipocyte-derived exosomes, alleviates inflammation and apoptosis of endothelial cells through suppressing TRADD expression [J] Eur J Pharmacol. 2020;872 doi: 10.1016/j.ejphar.2020.172977. [DOI] [PubMed] [Google Scholar]

[b0415] 83.Wang F., Chen F.F., Shang Y.Y., et al. Insulin resistance adipocyte-derived exosomes aggravate atherosclerosis by increasing vasa vasorum angiogenesis in diabetic ApoE(-/-) mice [J] Int J Cardiol. 2018;265:181–187. doi: 10.1016/j.ijcard.2018.04.028. [DOI] [PubMed] [Google Scholar]

[b0420] 84.Massberg S., Brand K., GRüNER S., et al. A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation [J] J Exp Med. 2002;196(7):887–896. doi: 10.1084/jem.20012044. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0425] 85.Huo Y., Schober A., Forlow S.B., et al. Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E [J] Nat Med. 2003;9(1):61–67. doi: 10.1038/nm810. [DOI] [PubMed] [Google Scholar]

[b0430] 86.Srikanthan S., Li W., Silverstein R.L., et al. Exosome poly-ubiquitin inhibits platelet activation, downregulates CD36 and inhibits pro-atherothombotic cellular functions [J] J Thrombosis Haemostasis: JTH. 2014;12(11):1906–1917. doi: 10.1111/jth.12712. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0435] 87.Li J., Tan M., Xiang Q., et al. Thrombin-activated platelet-derived exosomes regulate endothelial cell expression of ICAM-1 via microRNA-223 during the thrombosis-inflammation response [J] Thromb Res. 2017;154:96–105. doi: 10.1016/j.thromres.2017.04.016. [DOI] [PubMed] [Google Scholar]

[b0440] 88.Yao Y., Sun W., Sun Q., et al. Platelet-derived exosomal microRNA-25-3p inhibits coronary vascular endothelial cell inflammation through Adam10 via the NF-κB signaling pathway in ApoE(-/-) mice [J] Front Immunol. 2019;10:2205. doi: 10.3389/fimmu.2019.02205. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]

[b0445] 89.Lahmann A.L., Joner M. In-stent restenosis: chasing our tails in search of a solution [J] JACC Basic Translat Sci. 2020;5(1):12–14. doi: 10.1016/j.jacbts.2019.12.002. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0450] 90.Zou D., Yang P., Liu J., et al. Exosome-loaded pro-efferocytic vascular stent with Lp-PLA(2)-triggered release for preventing in-stent restenosis [J] ACS Nano. 2022;16(9):14925–14941. doi: 10.1021/acsnano.2c05847. [DOI] [PubMed] [Google Scholar]

[b0455] 91.Iyer D., Zhao Q., Wirka R., et al. Coronary artery disease genes SMAD3 and TCF21 promote opposing interactive genetic programs that regulate smooth muscle cell differentiation and disease risk [J] PLoS Genet. 2018;14(10):e1007681. doi: 10.1371/journal.pgen.1007681. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0460] 92.Gao X.F., Wang Z.M., Chen A.Q., et al. Plasma small extracellular vesicle-carried miRNA-501-5p promotes vascular smooth muscle cell phenotypic modulation-mediated in-stent restenosis [J] Oxid Med Cell Longev. 2021;2021:6644970. doi: 10.1155/2021/6644970. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0465] 93.Yan W., Li T., Yin T., et al. M2 macrophage-derived exosomes promote the c-KIT phenotype of vascular smooth muscle cells during vascular tissue repair after intravascular stent implantation [J] Theranostics. 2020;10(23):10712–10728. doi: 10.7150/thno.46143. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0470] 94.Thygesen K., Alpert J.S., Jaffe A.S., et al. Fourth universal definition of myocardial infarction (2018) [J] J Am Coll Cardiol. 2018;72(18):2231–2264. doi: 10.1016/j.jacc.2018.08.1038. [DOI] [PubMed] [Google Scholar]

[b0475] 95.Benjamin E.J., Muntner P., Alonso A., et al. Heart disease and stroke statistics-2019 update: a report from the American heart association [J] Circulation. 2019;139(10):e56–e528. doi: 10.1161/CIR.0000000000000659. [DOI] [PubMed] [Google Scholar]

[b0480] 96.JM V, DM Y, V S, et al. Plasma exosomes protect the myocardium from ischemia-reperfusion injury [J]. Journal of the American College of Cardiology, 2015, 65(15): 1525-36. [DOI] [PubMed]

[b0485] 97.Wang B., Cao C., Han D., et al. Dysregulation of miR-342-3p in plasma exosomes derived from convalescent AMI patients and its consequences on cardiac repair [J] Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2021;142 doi: 10.1016/j.biopha.2021.112056. [DOI] [PubMed] [Google Scholar]

[b0490] 98.Zhang Q., Wang L., Wang S., et al. Signaling pathways and targeted therapy for myocardial infarction [J] Signal Transduct Target Ther. 2022;7(1):78. doi: 10.1038/s41392-022-00925-z. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0495] 99.Jeong H., Choi D., Oh Y., et al. A nanocoating co-localizing nitric oxide and growth factor onto individual endothelial cells reveals synergistic effects on angiogenesis [J] Adv Healthc Mater. 2022;11(6):e2102095. doi: 10.1002/adhm.202102095. [DOI] [PubMed] [Google Scholar]

[b0500] 100.Li H., Liao Y., Gao L., et al. Coronary serum exosomes derived from patients with myocardial ischemia regulate angiogenesis through the mir-939-mediated nitric oxide signaling pathway [J] Theranostics. 2018;8(8):2079–2093. doi: 10.7150/thno.21895. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0505] 101.El-Hashemite N., Walker V., Zhang H., et al. Loss of Tsc1 or Tsc2 induces vascular endothelial growth factor production through mammalian target of rapamycin [J] Can Res. 2003;63(17):5173–5177. [PubMed] [Google Scholar]

[b0510] 102.Rattner A., Williams J., Nathans J. Roles of HIFs and VEGF in angiogenesis in the retina and brain [J] J Clin Invest. 2019;129(9):3807–3820. doi: 10.1172/JCI126655. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0515] 103.Tian X., Liu Y., Wang Z., et al. miR-144 delivered by nasopharyngeal carcinoma-derived EVs stimulates angiogenesis through the FBXW7/HIF-1α/VEGF-A axis [J] Mol Therapy Nucl Acids. 2021;24:1000–1011. doi: 10.1016/j.omtn.2021.03.016. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0520] 104.Duan S., Wang C., Xu X., et al. Peripheral serum exosomes isolated from patients with acute myocardial infarction promote endothelial cell angiogenesis via the miR-126-3p/TSC1/mTORC1/HIF-1α pathway [J] Int J Nanomed. 2022;17:1577–1592. doi: 10.2147/IJN.S338937. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0525] 105.Li H., Ding J., Liu W., et al. Plasma exosomes from patients with acute myocardial infarction alleviate myocardial injury by inhibiting ferroptosis through miR-26b-5p/SLC7A11 axis [J] Life Sci. 2023;322 doi: 10.1016/j.lfs.2023.121649. [DOI] [PubMed] [Google Scholar]

[b0530] 106.Prabhu S.D., Frangogiannis N.G. The biological basis for cardiac repair after myocardial infarction: from inflammation to fibrosis [J] Circ Res. 2016;119(1):91–112. doi: 10.1161/CIRCRESAHA.116.303577. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0535] 107.Ma Y., Yabluchanskiy A., Lindsey M.L. Neutrophil roles in left ventricular remodeling following myocardial infarction [J] Fibrogenesis Tissue Repair. 2013;6(1):11. doi: 10.1186/1755-1536-6-11. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0540] 108.Xiong Y.Y., Gong Z.T., Tang R.J., et al. The pivotal roles of exosomes derived from endogenous immune cells and exogenous stem cells in myocardial repair after acute myocardial infarction [J] Theranostics. 2021;11(3):1046–1058. doi: 10.7150/thno.53326. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0545] 109.Zlatanova I., Pinto C., Bonnin P., et al. Iron regulator hepcidin impairs macrophage-dependent cardiac repair after injury [J] Circulation. 2019;139(12):1530–1547. doi: 10.1161/CIRCULATIONAHA.118.034545. [DOI] [PubMed] [Google Scholar]

[b0550] 110.Mouton A J, DELEON-Pennell K Y, Rivera Gonzalez O J, et al. Mapping macrophage polarization over the myocardial infarction time continuum [J]. Basic research in cardiology, 2018, 113(4): 26. [DOI] [PMC free article] [PubMed]

[b0555] 111.Liu S., Chen J., Shi J., et al. M1-like macrophage-derived exosomes suppress angiogenesis and exacerbate cardiac dysfunction in a myocardial infarction microenvironment [J] Basic Res Cardiol. 2020;115(2):22. doi: 10.1007/s00395-020-0781-7. [DOI] [PubMed] [Google Scholar]

[b0560] 112.Koh W., Mahan R.D., Davis G.E. Cdc42- and Rac1-mediated endothelial lumen formation requires Pak2, Pak4 and Par3, and PKC-dependent signaling [J] J Cell Sci. 2008;121(Pt 7):989–1001. doi: 10.1242/jcs.020693. [DOI] [PubMed] [Google Scholar]

[b0565] 113.Wang C., Zhang C., Liu L., et al. Macrophage-derived mir-155-containing exosomes suppress fibroblast proliferation and promote fibroblast inflammation during cardiac injury [J] Mol Therapy: J Am Soc Gene Therapy. 2017;25(1):192–204. doi: 10.1016/j.ymthe.2016.09.001. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0570] 114.Long R., Gao L., Li Y., et al. M2 macrophage-derived exosomes carry miR-1271-5p to alleviate cardiac injury in acute myocardial infarction through down-regulating SOX6 [J] Mol Immunol. 2021;136:26–35. doi: 10.1016/j.molimm.2021.05.006. [DOI] [PubMed] [Google Scholar]

[b0575] 115.Ding J., Chen J., Wang Y., et al. Trbp regulates heart function through microRNA-mediated Sox6 repression [J] Nat Genet. 2015;47(7):776–783. doi: 10.1038/ng.3324. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0580] 116.Hu H., Wu J., Cao C., et al. Exosomes derived from regulatory T cells ameliorate acute myocardial infarction by promoting macrophage M2 polarization [J] IUBMB Life. 2020;72(11):2409–2419. doi: 10.1002/iub.2364. [DOI] [PubMed] [Google Scholar]

[b0585] 117.Zhu J., Yao K., Guo J., et al. miR-181a and miR-150 regulate dendritic cell immune inflammatory responses and cardiomyocyte apoptosis via targeting JAK1-STAT1/c-Fos pathway [J] J Cell Mol Med. 2017;21(11):2884–2895. doi: 10.1111/jcmm.13201. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0590] 118.Choo E.H., Lee J.H., Park E.H., et al. Infarcted myocardium-primed dendritic cells improve remodeling and cardiac function after myocardial infarction by modulating the regulatory T cell and macrophage polarization [J] Circulation. 2017;135(15):1444–1457. doi: 10.1161/CIRCULATIONAHA.116.023106. [DOI] [PubMed] [Google Scholar]

[b0595] 119.Liu H., Zhang Y., Yuan J., et al. Dendritic cell-derived exosomal miR-494-3p promotes angiogenesis following myocardial infarction [J] Int J Mol Med. 2021;47(1):315–325. doi: 10.3892/ijmm.2020.4776. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0600] 120.Li F., Wang Y., Lin L., et al. Mast cell-derived exosomes promote Th2 cell differentiation via OX40L-OX40 ligation [J] J Immunol Res. 2016;2016:3623898. doi: 10.1155/2016/3623898. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0605] 121.Peng Y., Zhao J.L., Peng Z.Y., et al. Exosomal miR-25-3p from mesenchymal stem cells alleviates myocardial infarction by targeting pro-apoptotic proteins and EZH2 [J] Cell Death Dis. 2020;11(5):317. doi: 10.1038/s41419-020-2545-6. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0610] 122.Sun L., Zhu W., Zhao P., et al. Long noncoding RNA UCA1 from hypoxia-conditioned hMSC-derived exosomes: a novel molecular target for cardioprotection through miR-873-5p/XIAP axis [J] Cell Death Dis. 2020;11(8):696. doi: 10.1038/s41419-020-02783-5. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0615] 123.Song Y., Wang B., Zhu X., et al. Human umbilical cord blood-derived MSCs exosome attenuate myocardial injury by inhibiting ferroptosis in acute myocardial infarction mice [J] Cell Biol Toxicol. 2021;37(1):51–64. doi: 10.1007/s10565-020-09530-8. [DOI] [PubMed] [Google Scholar]

[b0620] 124.Gong X.H., Liu H., Wang S.J., et al. Exosomes derived from SDF1-overexpressing mesenchymal stem cells inhibit ischemic myocardial cell apoptosis and promote cardiac endothelial microvascular regeneration in mice with myocardial infarction [J] J Cell Physiol. 2019;234(8):13878–13893. doi: 10.1002/jcp.28070. [DOI] [PubMed] [Google Scholar]

[b0625] 125.Mao Q., Liang X.L., Zhang C.L., et al. LncRNA KLF3-AS1 in human mesenchymal stem cell-derived exosomes ameliorates pyroptosis of cardiomyocytes and myocardial infarction through miR-138-5p/Sirt1 axis [J] Stem Cell Res Ther. 2019;10(1):393. doi: 10.1186/s13287-019-1522-4. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0630] 126.Xiao C., Wang K., Xu Y., et al. Transplanted mesenchymal stem cells reduce autophagic flux in infarcted hearts via the exosomal transfer of miR-125b [J] Circ Res. 2018;123(5):564–578. doi: 10.1161/CIRCRESAHA.118.312758. [DOI] [PubMed] [Google Scholar]

[b0635] 127.Sun J., Shen H., Shao L., et al. HIF-1α overexpression in mesenchymal stem cell-derived exosomes mediates cardioprotection in myocardial infarction by enhanced angiogenesis [J] Stem Cell Res Ther. 2020;11(1):373. doi: 10.1186/s13287-020-01881-7. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0640] 128.Wang S., Dong J., Li L., et al. Exosomes derived from miR-129-5p modified bone marrow mesenchymal stem cells represses ventricular remolding of mice with myocardial infarction [J] J Tissue Eng Regen Med. 2022;16(2):177–187. doi: 10.1002/term.3268. [DOI] [PubMed] [Google Scholar]

[b0645] 129.S B, L Z, L D, et al. Extracellular vesicles derived from human bone marrow mesenchymal stem cells promote angiogenesis in a rat myocardial infarction model [J]. J Mol Med (Berlin, Germany), 2014, 92(4): 387-97. [DOI] [PubMed]

[b0650] 130.Gao L., Mei S., Zhang S., et al. Cardio-renal exosomes in myocardial infarction serum regulate proangiogenic paracrine signaling in adipose mesenchymal stem cells [J] Theranostics. 2020;10(3):1060–1073. doi: 10.7150/thno.37678. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0655] 131.Liu D., Gu G., Gan L., et al. Identification of a CTRP9 C-Terminal polypeptide capable of enhancing bone-derived mesenchymal stem cell cardioprotection through promoting angiogenic exosome production [J] Redox Biol. 2021;41 doi: 10.1016/j.redox.2021.101929. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0660] 132.Hashemi S.M., Ghods S., Kolodgie F.D., et al. A placebo controlled, dose-ranging, safety study of allogenic mesenchymal stem cells injected by endomyocardial delivery after an acute myocardial infarction [J] Eur Heart J. 2008;29(2):251–259. doi: 10.1093/eurheartj/ehm559. [DOI] [PubMed] [Google Scholar]

[b0665] 133.Ning H., Chen H., Deng J., et al. Exosomes secreted by FNDC5-BMMSCs protect myocardial infarction by anti-inflammation and macrophage polarization via NF-κB signaling pathway and Nrf2/HO-1 axis [J] Stem Cell Res Ther. 2021;12(1):519. doi: 10.1186/s13287-021-02591-4. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0670] 134.Zhang J., Lu Y., Mao Y., et al. IFN-γ enhances the efficacy of mesenchymal stromal cell-derived exosomes via miR-21 in myocardial infarction rats [J] Stem Cell Res Ther. 2022;13(1):333. doi: 10.1186/s13287-022-02984-z. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0675] 135.Zheng H., Liang X., Han Q., et al. Hemin enhances the cardioprotective effects of mesenchymal stem cell-derived exosomes against infarction via amelioration of cardiomyocyte senescence [J] J Nanobiotechnol. 2021;19(1):332. doi: 10.1186/s12951-021-01077-y. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0680] 136.Zhu W., Sun L., Zhao P., et al. Macrophage migration inhibitory factor facilitates the therapeutic efficacy of mesenchymal stem cells derived exosomes in acute myocardial infarction through upregulating miR-133a-3p [J] J Nanobiotechnol. 2021;19(1):61. doi: 10.1186/s12951-021-00808-5. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0685] 137.Huang P., Wang L., Li Q., et al. Atorvastatin enhances the therapeutic efficacy of mesenchymal stem cells-derived exosomes in acute myocardial infarction via up-regulating long non-coding RNA H19 [J] Cardiovasc Res. 2020;116(2):353–367. doi: 10.1093/cvr/cvz139. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0690] 138.Su L.C., Xu W.D., Huang A.F. IRAK family in inflammatory autoimmune diseases [J] Autoimmun Rev. 2020;19(3) doi: 10.1016/j.autrev.2020.102461. [DOI] [PubMed] [Google Scholar]

[b0695] 139.Xiong Y., Tang R., Xu J., et al. Tongxinluo-pretreated mesenchymal stem cells facilitate cardiac repair via exosomal transfer of miR-146a-5p targeting IRAK1/NF-κB p65 pathway [J] Stem Cell Res Ther. 2022;13(1):289. doi: 10.1186/s13287-022-02969-y. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0700] 140.M K, E N, T A, et al. Embryonic stem cell-derived exosomes promote endogenous repair mechanisms and enhance cardiac function following myocardial infarction [J]. Circulation research, 2015, 117(1): 52-64. [DOI] [PMC free article] [PubMed]

[b0705] 141.Mazini L., Rochette L., Amine M., et al. Regenerative capacity of adipose derived stem cells (ADSCs), comparison with mesenchymal stem cells (MSCs) [J] Int J Mol Sci. 2019;20(10) doi: 10.3390/ijms20102523. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0710] 142.DE ALMEIDA OLIVEIRA N C, NERI E A, SILVA C M, et al. Multicellular regulation of miR-196a-5p and miR-425-5 from adipose stem cell-derived exosomes and cardiac repair [J]. Clinical science (London, England : 1979), 2022, 136(17): 1281-301. [DOI] [PubMed]

[b0715] 143.Zhu D., Wang Y., Thomas M., et al. Exosomes from adipose-derived stem cells alleviate myocardial infarction via microRNA-31/FIH1/HIF-1α pathway [J] J Mol Cell Cardiol. 2022;162:10–19. doi: 10.1016/j.yjmcc.2021.08.010. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0720] 144.Wang T., Li T., Niu X., et al. ADSC-derived exosomes attenuate myocardial infarction injury by promoting miR-205-mediated cardiac angiogenesis [J] Biol Direct. 2023;18(1):6. doi: 10.1186/s13062-023-00361-1. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0725] 145.Yue Y., Wang C., Benedict C., et al. Interleukin-10 deficiency alters endothelial progenitor cell-derived exosome reparative effect on myocardial repair via integrin-linked kinase enrichment [J] Circ Res. 2020;126(3):315–329. doi: 10.1161/CIRCRESAHA.119.315829. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0730] 146.Liu W., Feng Y., Wang X., et al. Human umbilical vein endothelial cells-derived exosomes enhance cardiac function after acute myocardial infarction by activating the PI3K/AKT signaling pathway [J] Bioengineered. 2022;13(4):8850–8865. doi: 10.1080/21655979.2022.2056317. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0735] 147.Yang Y., Li Y., Chen X., et al. Exosomal transfer of miR-30a between cardiomyocytes regulates autophagy after hypoxia [J] J Mol Med (Berl) 2016;94(6):711–724. doi: 10.1007/s00109-016-1387-2. [DOI] [PubMed] [Google Scholar]

[b0740] 148.Wang L., Zhang J. Exosomal lncRNA AK139128 derived from hypoxic cardiomyocytes promotes apoptosis and inhibits cell proliferation in cardiac fibroblasts [J] Int J Nanomed. 2020;15:3363–3376. doi: 10.2147/IJN.S240660. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0745] 149.Gou L., Xue C., Tang X., et al. Inhibition of Exo-miR-19a-3p derived from cardiomyocytes promotes angiogenesis and improves heart function in mice with myocardial infarction via targeting HIF-1α [J] Aging. 2020;12(23):23609–23618. doi: 10.18632/aging.103563. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0750] 150.Liao Z., Chen Y., Duan C., et al. Cardiac telocytes inhibit cardiac microvascular endothelial cell apoptosis through exosomal miRNA-21-5p-targeted cdip1 silencing to improve angiogenesis following myocardial infarction [J] Theranostics. 2021;11(1):268–291. doi: 10.7150/thno.47021. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0755] 151.A futile cycle in cell therapy [J]. Nat Biotechnol, 2017, 35(4): 291. [DOI] [PubMed]

[b0760] 152.Yanamandala M., Zhu W., Garry D.J., et al. Overcoming the roadblocks to cardiac cell therapy using tissue engineering [J] J Am Coll Cardiol. 2017;70(6):766–775. doi: 10.1016/j.jacc.2017.06.012. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0765] 153.Ye L., Chang Y.H., Xiong Q., et al. Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cells [J] Cell Stem Cell. 2014;15(6):750–761. doi: 10.1016/j.stem.2014.11.009. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0770] 154.Gao L., Wang Y., Wei P., Krishnamurthy G.P., Walcott P., Menasché J.Z. Erratum for the Research Article: “Exosomes secreted by hiPSC-derived cardiac cells improve recovery from myocardial infarction in swine” by L. [J] Sci Translat Med. 2020;12(567) doi: 10.1126/scitranslmed.aay1318. [DOI] [PubMed] [Google Scholar]

[b0775] 155.Gorski P.A., Ceholski D.K., Hajjar R.J. Altered myocardial calcium cycling and energetics in heart failure–a rational approach for disease treatment [J] Cell Metab. 2015;21(2):183–194. doi: 10.1016/j.cmet.2015.01.005. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0780] 156.Aoyama H., Ikeda Y., Miyazaki Y., et al. Isoform-specific roles of protein phosphatase 1 catalytic subunits in sarcoplasmic reticulum-mediated Ca(2+) cycling [J] Cardiovasc Res. 2011;89(1):79–88. doi: 10.1093/cvr/cvq252. [DOI] [PubMed] [Google Scholar]

[b0785] 157.Li H., Wang L., Ma T., et al. Exosomes secreted by endothelial cells derived from human induced pluripotent stem cells improve recovery from myocardial infarction in mice [J] Stem Cell Res Ther. 2023;14(1):278. doi: 10.1186/s13287-023-03462-w. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0790] 158.Yuan J., Yang H., Liu C., et al. Microneedle patch loaded with exosomes containing MicroRNA-29b prevents cardiac fibrosis after myocardial infarction [J] Adv Healthc Mater. 2023::e2202959. doi: 10.1002/adhm.202202959. [DOI] [PubMed] [Google Scholar]

[b0795] 159.Czosseck A., Chen M.M., Nguyen H., et al. Porous scaffold for mesenchymal cell encapsulation and exosome-based therapy of ischemic diseases [J] J Control Release. 2022;352:879–892. doi: 10.1016/j.jconrel.2022.10.057. [DOI] [PubMed] [Google Scholar]

[b0800] 160.Zhu D., Li Z., Huang K., et al. Minimally invasive delivery of therapeutic agents by hydrogel injection into the pericardial cavity for cardiac repair [J] Nat Commun. 2021;12(1):1412. doi: 10.1038/s41467-021-21682-7. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0805] 161.Liu S., Chen X., Bao L., et al. Treatment of infarcted heart tissue via the capture and local delivery of circulating exosomes through antibody-conjugated magnetic nanoparticles [J] Nat Biomed Eng. 2020;4(11):1063–1075. doi: 10.1038/s41551-020-00637-1. [DOI] [PubMed] [Google Scholar]

[b0810] 162.Yao J., Huang K., Zhu D., et al. A minimally invasive exosome spray repairs heart after myocardial infarction [J] ACS Nano. 2021;15(7):11099–11111. doi: 10.1021/acsnano.1c00628. [DOI] [PubMed] [Google Scholar]

[b0815] 163.Hu X., Ning X., Zhao Q., et al. Islet-1 mesenchymal stem cells-derived exosome-incorporated angiogenin-1 hydrogel for enhanced acute myocardial infarction therapy [J] ACS Appl Mater Interfaces. 2022;14(32):36289–36303. doi: 10.1021/acsami.2c04686. [DOI] [PubMed] [Google Scholar]

[b0820] 164.Lee J.R., Park B.W., Kim J., et al. Nanovesicles derived from iron oxide nanoparticles-incorporated mesenchymal stem cells for cardiac repair [J] Sci Adv. 2020;6(18):eaaz0952. doi: 10.1126/sciadv.aaz0952. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0825] 165.Ping P., Guan S., Ning C., et al. Fabrication of blended nanofibrous cardiac patch transplanted with TGF-β3 and human umbilical cord MSCs-derived exosomes for potential cardiac regeneration after acute myocardial infarction [J] Nanomed Nanotechnol Biol Med. 2023;54 doi: 10.1016/j.nano.2023.102708. [DOI] [PubMed] [Google Scholar]

[b0830] 166.Kazemi Asl S, Rahimzadegan M, Ostadrahimi R. The recent advancement in the chitosan hybrid-based scaffolds for cardiac regeneration after myocardial infarction [J]. Carbohydrate Polym 2023;300:120266. [DOI] [PubMed]

[b0835] 167.Shyu K.G., Wang B.W., Fang W.J., et al. Hyperbaric oxygen-induced long non-coding RNA MALAT1 exosomes suppress MicroRNA-92a expression in a rat model of acute myocardial infarction [J] J Cell Mol Med. 2020;24(22):12945–12954. doi: 10.1111/jcmm.15889. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0840] 168.Zhang X.J., Liu X., Hu M., et al. Pharmacological inhibition of arachidonate 12-lipoxygenase ameliorates myocardial ischemia-reperfusion injury in multiple species [J] Cell Metab. 2021;33(10):2059. doi: 10.1016/j.cmet.2021.08.014. [DOI] [PubMed] [Google Scholar]

[b0845] 169.Kamarauskaite J., Baniene R., Trumbeckas D., et al. Increased succinate accumulation induces ROS generation in in vivo ischemia/reperfusion-affected rat kidney mitochondria [J] Biomed Res Int. 2020;2020:8855585. doi: 10.1155/2020/8855585. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0850] 170.Fischer P., Hilfiker-Kleiner D. Survival pathways in hypertrophy and heart failure: the gp130-STAT3 axis [J] Basic Res Cardiol. 2007;102(4):279–297. doi: 10.1007/s00395-007-0658-z. [DOI] [PubMed] [Google Scholar]

[b0855] 171.Katsur M., He Z., Vinokur V., et al. Exosomes from neuronal stem cells may protect the heart from ischaemia/reperfusion injury via JAK1/2 and gp130 [J] J Cell Mol Med. 2021;25(9):4455–4465. doi: 10.1111/jcmm.16515. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0860] 172.Hu C., Liao J., Huang R., et al. MicroRNA-155-5p in serum derived-exosomes promotes ischaemia-reperfusion injury by reducing CypD ubiquitination by NEDD4 [J] ESC Heart Failure. 2023;10(2):1144–1157. doi: 10.1002/ehf2.14279. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0865] 173.Bei Y., Lu D., BäR C., et al. miR-486 attenuates cardiac ischemia/reperfusion injury and mediates the beneficial effect of exercise for myocardial protection [J] Mol Therapy: J Am Soc Gene Therapy. 2022;30(4):1675–1691. doi: 10.1016/j.ymthe.2022.01.031. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0870] 174.Ferreira P., Cravo M., Guerreiro C.S., et al. Fat intake interacts with polymorphisms of Caspase9, FasLigand and PPARgamma apoptotic genes in modulating Crohn's disease activity [J] Clin Nutrit (Edinburgh, Scotland) 2010;29(6):819–823. doi: 10.1016/j.clnu.2010.06.008. [DOI] [PubMed] [Google Scholar]

[b0875] 175.Chambers J.W., Pachori A., Howard S., et al. Inhibition of JNK mitochondrial localization and signaling is protective against ischemia/reperfusion injury in rats [J] J Biol Chem. 2013;288(6):4000–4011. doi: 10.1074/jbc.M112.406777. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0880] 176.Hou Z., Qin X., Hu Y., et al. Longterm exercise-derived exosomal miR-342-5p: A novel exerkine for cardioprotection [J] Circ Res. 2019;124(9):1386–1400. doi: 10.1161/CIRCRESAHA.118.314635. [DOI] [PubMed] [Google Scholar]

[b0885] 177.Dai Y., Wang S., Chang S., et al. M2 macrophage-derived exosomes carry microRNA-148a to alleviate myocardial ischemia/reperfusion injury via inhibiting TXNIP and the TLR4/NF-κB/NLRP3 inflammasome signaling pathway [J] J Mol Cell Cardiol. 2020;142:65–79. doi: 10.1016/j.yjmcc.2020.02.007. [DOI] [PubMed] [Google Scholar]

[b0890] 178.Zhai T.Y., Cui B.H., Zhou Y., et al. Exosomes released from CaSR-stimulated pmns reduce ischaemia/reperfusion injury [J] Oxid Med Cell Longev. 2021;2021:3010548. doi: 10.1155/2021/3010548. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0895] 179.Qin S.B., Peng D.Y., Lu J.M., et al. MiR-182-5p inhibited oxidative stress and apoptosis triggered by oxidized low-density lipoprotein via targeting toll-like receptor 4 [J] J Cell Physiol. 2018;233(10):6630–6637. doi: 10.1002/jcp.26389. [DOI] [PubMed] [Google Scholar]

[b0900] 180.Zilun W, Shuaihua Q, Jinxuan Z, et al. Corrigendum to “miRNA-181a over-expression in mesenchymal stem cell-derived exosomes influenced inflammatory response after myocardial ischemia-reperfusion injury. [Life Sci. 232 (2019) 116632] [J]. Life Sci, 2020, 256: 118045. [DOI] [PubMed]

[b0905] 181.Jia C., Chen H., Zhang J., et al. Role of pyroptosis in cardiovascular diseases [J] Int Immunopharmacol. 2019;67:311–318. doi: 10.1016/j.intimp.2018.12.028. [DOI] [PubMed] [Google Scholar]

[b0910] 182.Tang J., Jin L., Liu Y., et al. Exosomes derived from mesenchymal stem cells protect the myocardium against ischemia/reperfusion injury through inhibiting pyroptosis [J] Drug Des Devel Ther. 2020;14:3765–3775. doi: 10.2147/DDDT.S239546. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0915] 183.Chen G., Wang M., Ruan Z., et al. Mesenchymal stem cell-derived exosomal miR-143-3p suppresses myocardial ischemia-reperfusion injury by regulating autophagy [J] Life Sci. 2021;280 doi: 10.1016/j.lfs.2021.119742. [DOI] [PubMed] [Google Scholar]

[b0920] 184.Li Q., Bu Y., Shao H., et al. Protective effect of bone marrow mesenchymal stem cell-derived exosomes on cardiomyoblast hypoxia-reperfusion injury through the HAND2-AS1/miR-17-5p/Mfn2 axis [J] BMC Cardiovasc Disord. 2023;23(1):114. doi: 10.1186/s12872-023-03148-4. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0925] 185.Li K.S., Bai Y., Li J., et al. LncRNA HCP5 in hBMSC-derived exosomes alleviates myocardial ischemia reperfusion injury by sponging miR-497 to activate IGF1/PI3K/AKT pathway [J] Int J Cardiol. 2021;342:72–81. doi: 10.1016/j.ijcard.2021.07.042. [DOI] [PubMed] [Google Scholar]

[b0930] 186.Chen G., Yue A., Wang M., et al. The Exosomal lncRNA KLF3-AS1 from ischemic cardiomyocytes mediates IGF-1 secretion by mscs to rescue myocardial ischemia-reperfusion injury [J] Front. Cardiovascular Med. 2021;8 doi: 10.3389/fcvm.2021.671610. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0935] 187.DéRIJARD B, RAINGEAUD J, BARRETT T, et al. Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms [J]. Science (New York, NY), 1995, 267(5198): 682-5. [DOI] [PubMed]

[b0940] 188.Chen X., Zhu X., Liu Y., et al. Silencing of phospholipase C gamma 2 promotes proliferation of rat hepatocytes in vitro [J] J Cell Biochem. 2018;119(5):4085–4096. doi: 10.1002/jcb.26592. [DOI] [PubMed] [Google Scholar]

[b0945] 189.Wang Y., Shen Y. Exosomal miR-455-3p from BMMSCs prevents cardiac ischemia-reperfusion injury [J] Hum Exp Toxicol. 2022;41 doi: 10.1177/09603271221102508. [DOI] [PubMed] [Google Scholar]

[b0950] 190.Mao S., Zhao J., Zhang Z.J., et al. MiR-183-5p overexpression in bone mesenchymal stem cell-derived exosomes protects against myocardial ischemia/reperfusion injury by targeting FOXO1 [J] Immunobiology. 2022;227(3) doi: 10.1016/j.imbio.2022.152204. [DOI] [PubMed] [Google Scholar]

[b0955] 191.Jeyabal P., Thandavarayan R.A., Joladarashi D., et al. MicroRNA-9 inhibits hyperglycemia-induced pyroptosis in human ventricular cardiomyocytes by targeting ELAVL1 [J] Biochem Biophys Res Commun. 2016;471(4):423–429. doi: 10.1016/j.bbrc.2016.02.065. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0960] 192.Liu N., Xie L., Xiao P., et al. Cardiac fibroblasts secrete exosome microRNA to suppress cardiomyocyte pyroptosis in myocardial ischemia/reperfusion injury [J] Mol Cell Biochem. 2022;477(4):1249–1260. doi: 10.1007/s11010-021-04343-7. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0965] 193.Zhao Z.Q., Corvera J.S., Halkos M.E., et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning [J] Am J Physiol Heart Circ Physiol. 2003;285(2):H579–H588. doi: 10.1152/ajpheart.01064.2002. [DOI] [PubMed] [Google Scholar]

[b0970] 194.Luo H., Li X., Li T., et al. microRNA-423-3p exosomes derived from cardiac fibroblasts mediates the cardioprotective effects of ischaemic post-conditioning [J] Cardiovasc Res. 2019;115(7):1189–1204. doi: 10.1093/cvr/cvy231. [DOI] [PubMed] [Google Scholar]

[b0975] 195.L C, Y W, Y P, et al. Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury [J]. Biochemical and biophysical research communications, 2013, 431(3): 566-71. [DOI] [PMC free article] [PubMed]

[b0980] 196.Sun X.H., Wang X., Zhang Y., et al. Exosomes of bone-marrow stromal cells inhibit cardiomyocyte apoptosis under ischemic and hypoxic conditions via miR-486-5p targeting the PTEN/PI3K/AKT signaling pathway [J] Thromb Res. 2019;177:23–32. doi: 10.1016/j.thromres.2019.02.002. [DOI] [PubMed] [Google Scholar]

[b0985] 197.Duran J.M., Makarewich C.A., Sharp T.E., et al. Bone-derived stem cells repair the heart after myocardial infarction through transdifferentiation and paracrine signaling mechanisms [J] Circ Res. 2013;113(5):539–552. doi: 10.1161/CIRCRESAHA.113.301202. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0990] 198.Schena G.J., Murray E.K., Hildebrand A.N., et al. Cortical bone stem cell-derived exosomes' therapeutic effect on myocardial ischemia-reperfusion and cardiac remodeling [J] Am J Physiol Heart Circ Physiol. 2021;321(6):H1014–H1029. doi: 10.1152/ajpheart.00197.2021. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b0995] 199.Zhang Y., Wei L., Sun D., et al. Tanshinone IIA pretreatment protects myocardium against ischaemia/reperfusion injury through the phosphatidylinositol 3-kinase/Akt-dependent pathway in diabetic rats [J] Diabetes Obes Metab. 2010;12(4):316–322. doi: 10.1111/j.1463-1326.2009.01166.x. [DOI] [PubMed] [Google Scholar]

[b1000] 200.Zhang M.Q., Zheng Y.L., Chen H., et al. Sodium tanshinone IIA sulfonate protects rat myocardium against ischemia-reperfusion injury via activation of PI3K/Akt/FOXO3A/Bim pathway [J] Acta Pharmacol Sin. 2013;34(11):1386–1396. doi: 10.1038/aps.2013.91. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1005] 201.Fu M., Xie D., Sun Y., et al. Exosomes derived from MSC pre-treated with oridonin alleviates myocardial IR injury by suppressing apoptosis via regulating autophagy activation [J] J Cell Mol Med. 2021;25(12):5486–5496. doi: 10.1111/jcmm.16558. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1010] 202.Solazzo M., O'Brien F.J., Nicolosi V., et al. The rationale and emergence of electroconductive biomaterial scaffolds in cardiac tissue engineering [J] APL bioengineering. 2019;3(4) doi: 10.1063/1.5116579. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1015] 203.He X., Wang Q., Zhao Y., et al. Effect of intramyocardial grafting collagen scaffold with mesenchymal stromal cells in patients with chronic ischemic heart disease: a randomized clinical trial [J] JAMA Netw Open. 2020;3(9):e2016236. doi: 10.1001/jamanetworkopen.2020.16236. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1020] 204.Chen P., Wang L., Fan X., et al. Targeted delivery of extracellular vesicles in heart injury [J] Theranostics. 2021;11(5):2263–2277. doi: 10.7150/thno.51571. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1025] 205.Zou Y., Li L., Li Y., et al. Restoring cardiac functions after myocardial infarction-ischemia/reperfusion via an exosome anchoring conductive hydrogel [J] ACS Appl Mater Interfaces. 2021;13(48):56892–56908. doi: 10.1021/acsami.1c16481. [DOI] [PubMed] [Google Scholar]

[b1030] 206.Murphy SP, Ibrahim NE, Januzzi JL, JR. Heart failure with reduced ejection fraction: a review [J]. JAMA, 2020;324(5):488-504. [DOI] [PubMed]

[b1035] 207.Roger V.L. Epidemiology of heart failure: a contemporary perspective [J] Circ Res. 2021;128(10):1421–1434. doi: 10.1161/CIRCRESAHA.121.318172. [DOI] [PubMed] [Google Scholar]

[b1040] 208.Xue R., Tan W., Wu Y., et al. Role of exosomal miRNAs in heart failure [J] Front. Cardiovas. Med. 2020;7 doi: 10.3389/fcvm.2020.592412. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1045] 209.Akhmerov A., Parimon T. Extracellular vesicles, inflammation, and cardiovascular disease [J] Cells. 2022;11(14) doi: 10.3390/cells11142229. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1050] 210.Hulsmans M., Sager H.B., Roh J.D., et al. Cardiac macrophages promote diastolic dysfunction [J] J Exp Med. 2018;215(2):423–440. doi: 10.1084/jem.20171274. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1055] 211.Glezeva N., Voon V., Watson C., et al. Exaggerated inflammation and monocytosis associate with diastolic dysfunction in heart failure with preserved ejection fraction: evidence of M2 macrophage activation in disease pathogenesis [J] J Card Fail. 2015;21(2):167–177. doi: 10.1016/j.cardfail.2014.11.004. [DOI] [PubMed] [Google Scholar]

[b1060] 212.Natrus L., Labudzynskyi D., Muzychenko P., et al. Plasma-derived exosomes implement miR-126-associated regulation of cytokines secretion in PBMCs of CHF patients in vitro [J] Acta bio-medica : Atenei Parmensis. 2022;93(3):e2022066. doi: 10.23750/abm.v93i3.12449. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1065] 213.Díaz HS, Toledo C, Andrade D C, et al. Neuroinflammation in heart failure: new insights for an old disease [J]. J Physiol 2020;598(1):33-59. [DOI] [PubMed]

[b1070] 214.Kaye D.M., Lefkovits J., Jennings G.L., et al. Adverse consequences of high sympathetic nervous activity in the failing human heart [J] J Am Coll Cardiol. 1995;26(5):1257–1263. doi: 10.1016/0735-1097(95)00332-0. [DOI] [PubMed] [Google Scholar]

[b1075] 215.Ma A., Hong J., Shanks J., et al. Upregulating Nrf2 in the RVLM ameliorates sympatho-excitation in mice with chronic heart failure [J] Free Radic Biol Med. 2019;141:84–92. doi: 10.1016/j.freeradbiomed.2019.06.002. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1080] 216.Tan X., Jiao P.L., Wang Y.K., et al. The phosphoinositide-3 kinase signaling is involved in neuroinflammation in hypertensive rats [J] CNS Neurosci Ther. 2017;23(4):350–359. doi: 10.1111/cns.12679. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1085] 217.Wu K.L., Chan S.H., Chan J.Y. Neuroinflammation and oxidative stress in rostral ventrolateral medulla contribute to neurogenic hypertension induced by systemic inflammation [J] J Neuroinflammation. 2012;9:212. doi: 10.1186/1742-2094-9-212. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1090] 218.Saint-Pol J., Gosselet F., Duban-Deweer S., et al. Targeting and crossing the blood-brain barrier with extracellular vesicles [J] Cells. 2020;9(4) doi: 10.3390/cells9040851. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1095] 219.Xiao Y.C., Wang W., Gao Y., et al. The peripheral circulating exosomal microRNAs Related to central inflammation in chronic heart failure [J] J Cardiovasc Transl Res. 2022;15(3):500–513. doi: 10.1007/s12265-022-10266-5. [DOI] [PubMed] [Google Scholar]

[b1100] 220.Suzuki E., Fujita D., Takahashi M., et al. Therapeutic effects of mesenchymal stem cell-derived exosomes in cardiovascular disease [J] Adv Exp Med Biol. 2017;998:179–185. doi: 10.1007/978-981-10-4397-0_12. [DOI] [PubMed] [Google Scholar]

[b1105] 221.Li Q., Xu Y., Lv K., et al. Small extracellular vesicles containing miR-486-5p promote angiogenesis after myocardial infarction in mice and nonhuman primates [J] Sci Transl Med. 2021;13(584) doi: 10.1126/scitranslmed.abb0202. [DOI] [PubMed] [Google Scholar]

[b1110] 222.Guo Y., Yu Y., Hu S., et al. The therapeutic potential of mesenchymal stem cells for cardiovascular diseases [J] Cell Death Dis. 2020;11(5):349. doi: 10.1038/s41419-020-2542-9. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1115] 223.Tang J.N., Cores J., Huang K., et al. Concise review: is cardiac cell therapy dead? embarrassing trial outcomes and new directions for the future [J] Stem Cells Transl Med. 2018;7(4):354–359. doi: 10.1002/sctm.17-0196. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1120] 224.Wang X., Tang Y., Liu Z., et al. The application potential and advance of mesenchymal stem cell-derived exosomes in myocardial infarction [J] Stem Cells Int. 2021;2021:5579904. doi: 10.1155/2021/5579904. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1125] 225.Nakamura Y., Kita S., Tanaka Y., et al. Adiponectin stimulates exosome release to enhance mesenchymal stem-cell-driven therapy of heart failure in mice [J] Mol Therapy: J Am Soc Gene Therapy. 2020;28(10):2203–2219. doi: 10.1016/j.ymthe.2020.06.026. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1130] 226.Kita S., Maeda N., Shimomura I. Interorgan communication by exosomes, adipose tissue, and adiponectin in metabolic syndrome [J] J Clin Invest. 2019;129(10):4041–4049. doi: 10.1172/JCI129193. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1135] 227.AHN S, BASAVANA GOWDA M K, LEE M, et al. Novel linked butanolide dimer compounds increase adiponectin production during adipogenesis in human mesenchymal stem cells through peroxisome proliferator-activated receptor γ modulation [J]. European journal of medicinal chemistry, 2020, 187: 111969. [DOI] [PubMed]

[b1140] 228.Nabeebaccus A., Zheng S., Shah A.M. Heart failure-potential new targets for therapy [J] Br Med Bull. 2016;119(1):99–110. doi: 10.1093/bmb/ldw025. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1145] 229.Bayoumi A.S., Teoh J.P., Aonuma T., et al. MicroRNA-532 protects the heart in acute myocardial infarction, and represses prss23, a positive regulator of endothelial-to-mesenchymal transition [J] Cardiovasc Res. 2017;113(13):1603–1614. doi: 10.1093/cvr/cvx132. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1150] 230.Wang Z., Gao D., Wang S., et al. Exosomal microRNA-1246 from human umbilical cord mesenchymal stem cells potentiates myocardial angiogenesis in chronic heart failure [J] Cell Biol Int. 2021;45(11):2211–2225. doi: 10.1002/cbin.11664. [DOI] [PubMed] [Google Scholar]

[b1155] 231.Zhu X., Qiu C., Wang Y., et al. FGFR1 SUMOylation coordinates endothelial angiogenic signaling in angiogenesis [J] PNAS. 2022;119(26) doi: 10.1073/pnas.2202631119. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1160] 232.Sun P., Zhang K., Hassan S.H., et al. Endothelium-Targeted deletion of microRNA-15a/16-1 promotes poststroke angiogenesis and improves long-term neurological recovery [J] Circ Res. 2020;126(8):1040–1057. doi: 10.1161/CIRCRESAHA.119.315886. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1165] 233.RäSäNEN M, DEGERMAN J, NISSINEN T A, et al. VEGF-B gene therapy inhibits doxorubicin-induced cardiotoxicity by endothelial protection [J]. Proceedings of the National Academy of Sciences of the United States of America, 2016, 113(46): 13144-9. [DOI] [PMC free article] [PubMed]

[b1170] 234.Tian C., Yang Y., Bai B., et al. Potential of exosomes as diagnostic biomarkers and therapeutic carriers for doxorubicin-induced cardiotoxicity [J] Int J Biol Sci. 2021;17(5):1328–1338. doi: 10.7150/ijbs.58786. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1175] 235.Ni J., Liu Y., Kang L., et al. Human trophoblast-derived exosomes attenuate doxorubicin-induced cardiac injury by regulating miR-200b and downstream Zeb1 [J] J Nanobiotechnol. 2020;18(1):171. doi: 10.1186/s12951-020-00733-z. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1180] 236.Ding M., Shi R., Cheng S., et al. Mfn2-mediated mitochondrial fusion alleviates doxorubicin-induced cardiotoxicity with enhancing its anticancer activity through metabolic switch [J] Redox Biol. 2022;52 doi: 10.1016/j.redox.2022.102311. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1185] 237.Duan J., Liu X., Shen S., et al. Trophoblast Stem-Cell-Derived Exosomes Alleviate Cardiotoxicity of Doxorubicin via Improving Mfn2-Mediated Mitochondrial Fusion [J] Cardiovasc Toxicol. 2023;23(1):23–31. doi: 10.1007/s12012-022-09774-2. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1190] 238.Pang Y., Ma M., Wang D., et al. Embryonic stem cell-derived exosomes attenuate transverse aortic constriction induced heart failure by increasing angiogenesis [J] Front Cardiovasc Med. 2021;8 doi: 10.3389/fcvm.2021.638771. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1195] 239.Liu M, López De Juan Abad B, Cheng K. Cardiac fibrosis: Myofibroblast-mediated pathological regulation and drug delivery strategies [J]. Adv Drug Del Rev 2021;173:504-19. [DOI] [PMC free article] [PubMed]

[b1200] 240.Liang T., Gao F., Jiang J., et al. Loss of phosphatase and Tensin homolog promotes cardiomyocyte proliferation and cardiac repair after myocardial infarction [J] Circulation. 2020;142(22):2196–2199. doi: 10.1161/CIRCULATIONAHA.120.046372. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1205] 241.Hu H.H., Chen D.Q., Wang Y.N., et al. New insights into TGF-β/Smad signaling in tissue fibrosis [J] Chem Biol Interact. 2018;292:76–83. doi: 10.1016/j.cbi.2018.07.008. [DOI] [PubMed] [Google Scholar]

[b1210] 242.Song J., Zhu Y., Li J., et al. Pellino1-mediated TGF-β1 synthesis contributes to mechanical stress induced cardiac fibroblast activation [J] J Mol Cell Cardiol. 2015;79:145–156. doi: 10.1016/j.yjmcc.2014.11.006. [DOI] [PubMed] [Google Scholar]

[b1215] 243.Tang C., Hou Y.X., Shi P.X., et al. Cardiomyocyte-specific Peli1 contributes to the pressure overload-induced cardiac fibrosis through miR-494-3p-dependent exosomal communication [J] FASEB J. 2023;37(1):e22699. doi: 10.1096/fj.202200597R. [DOI] [PubMed] [Google Scholar]

[b1220] 244.Bittle G.J., Morales D., Pietris N., et al. Exosomes isolated from human cardiosphere-derived cells attenuate pressure overload-induced right ventricular dysfunction [J] J Thorac Cardiovasc Surg. 2021;162(3):975. doi: 10.1016/j.jtcvs.2020.06.154. [DOI] [PubMed] [Google Scholar]

[b1225] 245.Jenča D, Melenovský V, Stehlik J, et al. Heart failure after myocardial infarction: incidence and predictors [J]. ESC Heart Failure, 2021; 8(1): 222-37. [DOI] [PMC free article] [PubMed]

[b1230] 246.Yang J., Yang J., Gong X., et al. Recent progress in microneedles-mediated diagnosis, therapy, and theranostic systems [J] Adv Healthc Mater. 2022;11(10):e2102547. doi: 10.1002/adhm.202102547. [DOI] [PubMed] [Google Scholar]

[b1235] 247.Ohayon L., Zhang X., Dutta P. The role of extracellular vesicles in regulating local and systemic inflammation in cardiovascular disease [J] Pharmacol Res. 2021;170 doi: 10.1016/j.phrs.2021.105692. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1240] 248.Hausenloy D.J., Yellon D.M. Ischaemic conditioning and reperfusion injury [J] Nat Rev Cardiol. 2016;13(4):193–209. doi: 10.1038/nrcardio.2016.5. [DOI] [PubMed] [Google Scholar]

[b1245] 249.Ma L.L., Ding Z.W., Yin P.P., et al. Hypertrophic preconditioning cardioprotection after myocardial ischaemia/reperfusion injury involves ALDH2-dependent metabolism modulation [J] Redox Biol. 2021;43 doi: 10.1016/j.redox.2021.101960. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1250] 250.Seeger J.P., Benda N.M., Riksen N.P., et al. Heart failure is associated with exaggerated endothelial ischaemia-reperfusion injury and attenuated effect of ischaemic preconditioning [J] Eur J Prev Cardiol. 2016;23(1):33–40. doi: 10.1177/2047487314558377. [DOI] [PubMed] [Google Scholar]

[b1255] 251.Luo Z., Hu X., Wu C., et al. Plasma exosomes generated by ischaemic preconditioning are cardioprotective in a rat heart failure model [J] Br J Anaesth. 2023;130(1):29–38. doi: 10.1016/j.bja.2022.08.040. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1260] 252.Yong S.B., Song Y., Kim H.J., et al. Mononuclear phagocytes as a target, not a barrier, for drug delivery [J] J Control Release. 2017;259:53–61. doi: 10.1016/j.jconrel.2017.01.024. [DOI] [PubMed] [Google Scholar]

[b1265] 253.Wan Z., Zhao L., Lu F., et al. Mononuclear phagocyte system blockade improves therapeutic exosome delivery to the myocardium [J] Theranostics. 2020;10(1):218–230. doi: 10.7150/thno.38198. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1270] 254.Zang H., Wu W., Qi L., et al. Autophagy inhibition enables Nrf2 to exaggerate the progression of diabetic cardiomyopathy in mice [J] Diabetes. 2020;69(12):2720–2734. doi: 10.2337/db19-1176. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1275] 255.Jia G., Demarco V.G., Sowers J.R. Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy [J] Nat Rev Endocrinol. 2016;12(3):144–153. doi: 10.1038/nrendo.2015.216. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1280] 256.Dewanjee S., Vallamkondu J., Kalra R.S., et al. Autophagy in the diabetic heart: A potential pharmacotherapeutic target in diabetic cardiomyopathy [J] Ageing Res Rev. 2021;68 doi: 10.1016/j.arr.2021.101338. [DOI] [PubMed] [Google Scholar]

[b1285] 257.Tong M., Saito T., Zhai P., et al. Mitophagy is essential for maintaining cardiac function during high fat diet-induced diabetic cardiomyopathy [J] Circ Res. 2019;124(9):1360–1371. doi: 10.1161/CIRCRESAHA.118.314607. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1290] 258.Yao Q., Ke Z.Q., Guo S., et al. Curcumin protects against diabetic cardiomyopathy by promoting autophagy and alleviating apoptosis [J] J Mol Cell Cardiol. 2018;124:26–34. doi: 10.1016/j.yjmcc.2018.10.004. [DOI] [PubMed] [Google Scholar]

[b1295] 259.Zhu Y., Qian X., Li J., et al. Astragaloside-IV protects H9C2(2–1) cardiomyocytes from high glucose-induced injury via miR-34a-mediated autophagy pathway [J] Artif Cells Nanomed Biotechnol. 2019;47(1):4172–4181. doi: 10.1080/21691401.2019.1687492. [DOI] [PubMed] [Google Scholar]

[b1300] 260.Cui W., Hao Y., Wang M., et al. Inhibition of autophagy facilitates XY03-EA-mediated neuroprotection against the cerebral ischemia/reperfusion injury in rats [J] Oxid Med Cell Longev. 2022;2022:7013299. doi: 10.1155/2022/7013299. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1305] 261.Richter K., Haslbeck M., Buchner J. The heat shock response: life on the verge of death [J] Mol Cell. 2010;40(2):253–266. doi: 10.1016/j.molcel.2010.10.006. [DOI] [PubMed] [Google Scholar]

[b1310] 262.Wang X., Gu H., Huang W., et al. Hsp20-mediated activation of exosome biogenesis in cardiomyocytes improves cardiac function and angiogenesis in diabetic mice [J] Diabetes. 2016;65(10):3111–3128. doi: 10.2337/db15-1563. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1315] 263.Pattingre S., Tassa A., Qu X., et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy [J] Cell. 2005;122(6):927–939. doi: 10.1016/j.cell.2005.07.002. [DOI] [PubMed] [Google Scholar]

[b1320] 264.Liang X.H., Jackson S., Seaman M., et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1 [J] Nature. 1999;402(6762):672–676. doi: 10.1038/45257. [DOI] [PubMed] [Google Scholar]

[b1325] 265.Levine B., Sinha S., Kroemer G. Bcl-2 family members: dual regulators of apoptosis and autophagy [J] Autophagy. 2008;4(5):600–606. doi: 10.4161/auto.6260. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1330] 266.He C., Zhu H., Li H., et al. Dissociation of Bcl-2-Beclin1 complex by activated AMPK enhances cardiac autophagy and protects against cardiomyocyte apoptosis in diabetes [J] Diabetes. 2013;62(4):1270–1281. doi: 10.2337/db12-0533. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1335] 267.Hu J., Wang S., Xiong Z., et al. Exosomal Mst1 transfer from cardiac microvascular endothelial cells to cardiomyocytes deteriorates diabetic cardiomyopathy [J] Biochim Biophys Acta. 2018;1864(11):3639–3649. doi: 10.1016/j.bbadis.2018.08.026. [DOI] [PubMed] [Google Scholar]

[b1340] 268.Krishnamurthy P., Rajasingh J., Lambers E., et al. IL-10 inhibits inflammation and attenuates left ventricular remodeling after myocardial infarction via activation of STAT3 and suppression of HuR [J] Circ Res. 2009;104(2):e9–e. doi: 10.1161/CIRCRESAHA.108.188243. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1345] 269.Govindappa P.K., Patil M., Garikipati V.N.S., et al. Targeting exosome-associated human antigen R attenuates fibrosis and inflammation in diabetic heart [J] FASEB J. 2020;34(2):2238–2251. doi: 10.1096/fj.201901995R. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1350] 270.Wei B., Lu F., Kong Q., et al. Trehalose induces B cell autophagy to alleviate myocardial injury via the AMPK/ULK1 signalling pathway in acute viral myocarditis induced by Coxsackie virus B3 [J] Int J Biochem Cell Biol. 2022;146 doi: 10.1016/j.biocel.2022.106208. [DOI] [PubMed] [Google Scholar]

[b1355] 271.Zhang Z., Chen L., Chen X., et al. Exosomes derived from human umbilical cord mesenchymal stem cells (HUCMSC-EXO) regulate autophagy through AMPK-ULK1 signaling pathway to ameliorate diabetic cardiomyopathy [J] Biochem Biophys Res Commun. 2022;632:195–203. doi: 10.1016/j.bbrc.2022.10.001. [DOI] [PubMed] [Google Scholar]

[b1360] 272.Xiong J., Hu H., Guo R., et al. Mesenchymal stem cell exosomes as a new strategy for the treatment of diabetes complications [J] Front Endocrinol. 2021;12 doi: 10.3389/fendo.2021.646233. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1365] 273.Lee J.Y., Chung J., Byun Y., et al. Mesenchymal stem cell-derived small extracellular vesicles protect cardiomyocytes from doxorubicin-induced cardiomyopathy by upregulating survivin expression via the miR-199a-3p-Akt-Sp1/p53 signaling pathway [J] Int J Mol Sci. 2021;22(13) doi: 10.3390/ijms22137102. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1370] 274.Milano G., Biemmi V., Lazzarini E., et al. Intravenous administration of cardiac progenitor cell-derived exosomes protects against doxorubicin/trastuzumab-induced cardiac toxicity [J] Cardiovasc Res. 2020;116(2):383–392. doi: 10.1093/cvr/cvz108. [DOI] [PubMed] [Google Scholar]

[b1375] 275.Pollack A., Kontorovich A.R., Fuster V., et al. Viral myocarditis–diagnosis, treatment options, and current controversies [J] Nat Rev Cardiol. 2015;12(11):670–680. doi: 10.1038/nrcardio.2015.108. [DOI] [PubMed] [Google Scholar]

[b1380] 276.Caforio A.L., Pankuweit S., Arbustini E., et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases [J] Eur Heart J. 2013;34(33) doi: 10.1093/eurheartj/eht210. [DOI] [PubMed] [Google Scholar]

[b1385] 277.Zhao H., Shang Q., Pan Z., et al. Exosomes from adipose-derived stem cells attenuate adipose inflammation and obesity through polarizing M2 macrophages and beiging in white adipose tissue [J] Diabetes. 2018;67(2):235–247. doi: 10.2337/db17-0356. [DOI] [PubMed] [Google Scholar]

[b1390] 278.Gu X., Li Y., Chen K., et al. Exosomes derived from umbilical cord mesenchymal stem cells alleviate viral myocarditis through activating AMPK/mTOR-mediated autophagy flux pathway [J] J Cell Mol Med. 2020;24(13):7515–7530. doi: 10.1111/jcmm.15378. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1395] 279.Sun P., Wang N., Zhao P., et al. Circulating exosomes control CD4(+) T cell immunometabolic functions via the transfer of miR-142 as a novel mediator in myocarditis [J] Mol Therapy: J Am Soc Gene Therapy. 2020;28(12):2605–2620. doi: 10.1016/j.ymthe.2020.08.015. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1400] 280.Wang Y, Jin P, Liu J, et al. Exosomal microRNA-122 mediates obesity-related cardiomyopathy through suppressing mitochondrial ADP-ribosylation factor-like 2 [J]. Clinical science (London, England: 1979), 2019, 133(17): 1871-81. [DOI] [PubMed]

[b1405] 281.Gartz M., Lin C.W., Sussman M.A., et al. Duchenne muscular dystrophy (DMD) cardiomyocyte-secreted exosomes promote the pathogenesis of DMD-associated cardiomyopathy [J] Dis Model Mech. 2020;13(11) doi: 10.1242/dmm.045559. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1410] 282.Li F., Zhang K., Xu T., et al. Exosomal microRNA-29a mediates cardiac dysfunction and mitochondrial inactivity in obesity-related cardiomyopathy [J] Endocrine. 2019;63(3):480–488. doi: 10.1007/s12020-018-1753-7. [DOI] [PubMed] [Google Scholar]

[b1415] 283.Vandergriff A., Huang K., Shen D., et al. Targeting regenerative exosomes to myocardial infarction using cardiac homing peptide [J] Theranostics. 2018;8(7):1869–1878. doi: 10.7150/thno.20524. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1420] 284.Luan X., Sansanaphongpricha K., Myers I., et al. Engineering exosomes as refined biological nanoplatforms for drug delivery [J] Acta Pharmacol Sin. 2017;38(6):754–763. doi: 10.1038/aps.2017.12. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1425] 285.Huang K., Ozpinar E.W., Su T., et al. An off-the-shelf artificial cardiac patch improves cardiac repair after myocardial infarction in rats and pigs [J] Sci Transl Med. 2020;12(538) doi: 10.1126/scitranslmed.aat9683. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1430] 286.Tang J., Wang J., Huang K., et al. Cardiac cell-integrated microneedle patch for treating myocardial infarction [J] Sci Adv. 2018;4(11):eaat9365. doi: 10.1126/sciadv.aat9365. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1435] 287.Cannata A., Petrella D., Russo C.F., et al. Postsurgical intrapericardial adhesions: mechanisms of formation and prevention [J] Ann Thorac Surg. 2013;95(5):1818–1826. doi: 10.1016/j.athoracsur.2012.11.020. [DOI] [PubMed] [Google Scholar]

[b1440] 288.Cheng G., Zhu D., Huang K., et al. Minimally invasive delivery of a hydrogel-based exosome patch to prevent heart failure [J] J Mol Cell Cardiol. 2022;169:113–121. doi: 10.1016/j.yjmcc.2022.04.020. [DOI] [PubMed] [Google Scholar]

[b1445] 289.Huang J.P., Chang C.C., Kuo C.Y., et al. Exosomal microRNAs miR-30d-5p and miR-126a-5p are associated with heart failure with preserved ejection fraction in STZ-induced type 1 diabetic rats [J] Int J Mol Sci. 2022;23(14) doi: 10.3390/ijms23147514. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1450] 290.Kang J.Y., Mun D., Kim H., et al. Serum exosomal long noncoding RNAs as a diagnostic biomarker for atrial fibrillation [J] Heart Rhythm. 2022;19(9):1450–1458. doi: 10.1016/j.hrthm.2022.05.033. [DOI] [PubMed] [Google Scholar]

[b1455] 291.Wang Y., Liang J., Xu J., et al. Circulating exosomes and exosomal lncRNA HIF1A-AS1 in atherosclerosis [J] Int J Clin Exp Path. 2017;10(8):8383–8388. [PMC free article] [PubMed] [Google Scholar]

[b1460] 292.Liang C., Zhang L., Lian X., et al. Circulating exosomal SOCS2-AS1 acts as a novel biomarker in predicting the diagnosis of coronary artery disease [J] Biomed Res Int. 2020;2020:9182091. doi: 10.1155/2020/9182091. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1465] 293.Zheng M.L., Liu X.Y., Han R.J., et al. Circulating exosomal long non-coding RNAs in patients with acute myocardial infarction [J] J Cell Mol Med. 2020;24(16):9388–9396. doi: 10.1111/jcmm.15589. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1470] 294.Bai C., Liu Y., Zhao Y., et al. Circulating exosome-derived miR-122-5p is a novel biomarker for prediction of postoperative atrial fibrillation [J] J Cardiovasc Transl Res. 2022;15(6):1393–1405. doi: 10.1007/s12265-022-10267-4. [DOI] [PubMed] [Google Scholar]

[b1475] 295.Chang S.N., Chen J.J., Wu J.H., et al. Association between exosomal miRNAs and coronary artery disease by next-generation sequencing [J] Cells. 2021;11(1) doi: 10.3390/cells11010098. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1480] 296.Zhang P., Liang T., Chen Y., et al. Circulating exosomal miRNAs as novel biomarkers for stable coronary artery disease [J] Biomed Res Int. 2020;2020:3593962. doi: 10.1155/2020/3593962. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b1485] 297.Wu W.P., Pan Y.H., Cai M.Y., et al. Plasma-derived exosomal circular RNA hsa_circ_0005540 as a novel diagnostic biomarker for coronary artery disease [J] Dis Markers. 2020;2020:3178642. doi: 10.1155/2020/3178642. [DOI] [PMC free article] [PubMed] [Google Scholar]

PERMALINK

Advances in the study of exosomes in cardiovascular diseases

Zhaobo Zhang

Yuanming Zou

Chunyu Song

Kexin Cao

Kexin Cai

Shuxian Chen

Yanjiao Wu

Danxi Geng

Guozhe Sun

Naijin Zhang

Xingang Zhang

Yixiao Zhang

Yingxian Sun

Ying Zhang

Graphical abstract

Highlights

Abstract

Background

Aim of review

Key scientific concepts of review

Introduction

Biogenesis, composition, mechanisms, and functions of exosomes

The relationship between exosomes and cardiovascular diseases

Fig. 1.

Fig. 2.

Fig. 3.

Table 1.

Summary and outlook

Funding Statement

Declaration of Competing Interest

Acknowledgements

Biographies

Contributor Information

References

ACTIONS

PERMALINK

RESOURCES

Similar articles

Cited by other articles

Links to NCBI Databases