Table 1.
Summary of exosomes derived from different cell sources in cardiovascular diseases.
| Source | Cargos | Biological effects | Evidences | References |
|---|---|---|---|---|
| Cardiomyocytes | HSP20 | Promote angiogenesis by activating VEGFR2, and activate AKT signaling pathway and repress TNF-α and IL-1β factors to alleviate myocardial infarction | Preclinical evidences (in vivo and in vitro) | [20, 21] |
| HSP60 | Promote immune responses | Preclinical evidences (in vitro) | [23] | |
| HSP70 | Activate monocytes alone, resulting in monocyte adhesion to endothelial cells; improve cardiac function | Preclinical evidences (in vitro) | [16, 17] | |
| HSP90 and IL-6 | Active STAT-3 signaling in cardiac fibroblasts that culminates in excess collagen synthesis, leading to severely compromised cardiac function during cardiac hypertrophy | Preclinical evidences (in vivo and in vitro) | [24] | |
| TNF-α | Interact with HIF-1α to contribute to cardiac remodeling | Preclinical evidences (in vitro) | [25] | |
| GLUT | Increase glucose transport | Preclinical evidences (in vitro) | [26] | |
| miR-15b, miR-17, miR-20a, miR-103, miR-199a, miR-210, and miR-292 | Enhance angiogenesis, reduce profibrotic gene expression, preserve myocardial contractile function, and improve cardiac function | Preclinical evidences (in vivo and in vitro) | [90] | |
| miR-29b, miR-323-5p, miR-455, and miR-466 | Mediate the regulation of MMP9, which is involved in matrix degradation and leads to fibrosis and myocyte uncoupling | Preclinical evidences (in vitro) | [31] | |
| miR-30a | Regulate autophagy by affecting the expression of Beclin-1, ATG12, and the ratio of LC3II/LC3I | Preclinical evidences (in vitro) | [30] | |
| miR-34a | Biomarkers of myocardial infarction | Preclinical evidences (in vitro) | [14] | |
| miR-146a | Inhibit apoptosis and promote proliferation of cardiomyocytes, while enhancing angiogenesis | Preclinical evidences (in vivo and in vitro) | [27] | |
| miR-208a | Increase fibroblast proliferation and differentiation into myofibroblasts via targeting Dyrk2 | Preclinical evidences (in vivo and in vitro) | [32] | |
| miR-320 | Inhibit proliferation, migration, and tube-like formation | Preclinical evidences (in vivo and in vitro) | [29] | |
| miR-451 | Protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation and inhibit cardiomyocyte apoptosis | Preclinical evidences (in vivo and in vitro) | [39] | |
| NA | Reduce apoptosis and fibrosis | Preclinical evidences (in vivo and in vitro) | [28] | |
| NA | Activate fibroblasts, which can increase the secretion of angiogenic factor, SDF1 and VEGF by fibroblasts | Preclinical evidences (in vivo and in vitro) | [33, 34] | |
| NA | Promote angiogenesis and cardiac protection | Preclinical evidences (in vivo and in vitro) | [34] | |
|
| ||||
| Cardiac progenitor cells | PAPP-A | Cardioprotection profile through releasing IGF-1 via proteolytic cleavage of IGFBP-4, resulting in IGF-1R activation, intracellular Akt and ERK1/2 phosphorylation | Preclinical evidences (in vivo and in vitro) | [87] |
| miR-15b and miR-20a | Stimulate angiogenesis | Preclinical evidences (in vivo and in vitro) | [38] | |
| miR-17 and miR-103 | Promote angiogenesis, inhibit myocardial fibrosis | Preclinical evidences (in vivo and in vitro) | [38] | |
| miR-21 | Inhibit cardiomyocyte apoptosis through downregulating PDCD4; downregulate both infarction size and injury marker expressions in vivo and promote endothelial cell proliferation, inhibit the apoptosis, and stimulate angiogenesis in vitro by targeting PTEN | Preclinical evidences (in vivo and in vitro) | [41, 42] | |
| miR-126 and miR-210 |
Active kinase and induce glycolysis | Preclinical evidences (in vivo and in vitro) | [40] | |
| miR-132, miR-210, and miR-146a-3p | Decrease myocardial apoptosis, increase angiogenesis, and improve left ventricular ejection fraction | Preclinical evidences (in vivo and in vitro) | [27, 36, 37] | |
| miR-133a | Improve cardiac function by reducing fibrosis and hypertrophy and increasing vascularization and cardiomyocyte proliferation | Preclinical evidences (in vivo and in vitro) | [44] | |
| miR-146a-5p | Attenuate doxorubicin/trastuzumab-induced oxidative stress in cardiomyocytes through suppressing target genes Traf6, Smad4, Irak1, Nox4, and Mpo | Clinical evidences | [43] | |
| miR-181a and miR-323-5p | Promote angiogenesis | Preclinical evidences (in vivo and in vitro) | [27, 36] | |
| miR-210 | Promote angiogenesis, inhibit cardiomyocyte apoptosis, improve heart function | Preclinical evidences (in vivo and in vitro) | [38] | |
| lnc RNA MALAT1 | Promote the infarct healing through improvement of cardiomyocyte survival and angiogenesis by targeting the miRNA | Preclinical evidences (in vivo and in vitro) | [45] | |
| NA | Stimulate cell migration | Preclinical evidences (in vitro) | [46] | |
|
| ||||
| Fibroblasts | miR-21-3p | Induce cardiomyocyte hypertrophy by targeting SORBS2 and PDLIM5 | Preclinical evidences (in vivo and in vitro) | [47] |
| miR-21, miR-29, and miR-30 | Biomarkers of left ventricular hypertrophy | Preclinical evidences (in vivo and in vitro) | [48] | |
| miR-34a | Biomarkers of myocardial infarction | Preclinical evidences (in vitro) | [14] | |
|
| ||||
| Mesenchymal stem cells | NA | Reduce the infarct area, inhibit the proliferation and migration of vascular smooth muscle, reduce cardiomyocyte apoptosis, promote angiogenesis, reduce ventricular remodeling, and protect cardiac function | Preclinical evidences (in vivo and in vitro) | [52–55] |
| NA | Protect cardiomyocytes from apoptosis through lncRNA-NEAT1/miR-142-3p/FOXO1 signaling pathway | Preclinical evidences (in vitro) | [56, 57] | |
| NA | Reduce the levels of inflammatory factors, such as IL-6 and MCP-1, through activating the signal pathways involved in IGF-1/PI3K/Akt and GSK-3p | Preclinical evidences (in vivo and in vitro) | [52–54, 58, 59] | |
| NA | Inhibit vascular remodeling and hypertension by inhibiting STAT3 signaling pathway | Preclinical evidences (in vivo and in vitro) | [60] | |
| NA | Reverse pulmonary hypertension | Preclinical evidences (in vivo) | [61] | |
| miR-126 and miR-130a | Biomarkers of chronic heart failure | Clinical evidences | [67] | |
| miR-294 | Increase neovascularization, cardiomyocyte survival, and reduce fibrosis | Preclinical evidences (in vivo and in vitro) | [66] | |
|
| ||||
| Endothelial cells | KLF2 | Attenuate the formation of atherosclerosis | Preclinical evidences (in vivo and in vitro) | [49] |
| miR-10b-5p | Ameliorate cardiac fibroblast activation | Preclinical evidences (in vitro) | [89] | |
| miR-146a-5p and miR-146b-5p | Inhibit the migration and angiogenesis | Preclinical evidences (in vitro) | [88] | |
|
| ||||
| Macrophages and leukocyte | NA | Promote vascular smooth muscle cells migration and adhesion, which may be mediated by the integration of extracellular vesicles into vascular smooth muscle cells and the subsequent downstream activation of ERK and Akt | Preclinical evidences (in vitro) | [51] |
| Biomarkers of atherosclerosis | Clinical evidences | [50] | ||
| Cardiac stromal cells | miR-21-5p | Contribute to heart repair by enhancing angiogenesis and cardiomyocyte survival through the phosphatase and tensin homolog/Akt pathway | Pre-clinical evidences (in vivo and in vitro) | [93] |