From pollution to palpitations: the heart’s silent battle with microplastics

Abstract

The pervasive presence of microplastics and nanoplastics (MNPs) in the environment has raised growing concerns regarding their potential health impacts. While research has progressively revealed the toxicological effects of MNPs, limited attention has been given to their specific influence on the cardiovascular system, particularly in human models. This systematic review synthesizes current evidence on MNP-induced cardiotoxicity, highlighting both physiological outcomes and underlying mechanisms.

A total of 72 studies—including in vivo experiments on aquatic species and rodents, and in vitro assays on human cardiovascular cells—were analyzed. The findings consistently demonstrate that MNPs can impair cardiac function by altering heart rate, inducing pericardial edema, and promoting myocardial fibrosis. These effects are mediated by mechanisms such as oxidative stress, inflammation, apoptosis, and disruptions in cellular signaling pathways.

Toxicity outcomes vary based on particle characteristics (type, size, and surface chemistry), exposure dose and duration, organismal factors (age, sex, species), and co-exposure to other pollutants. Notably, smaller particles (< 100 nm) exhibit greater bioaccumulation and systemic penetration, correlating with higher cardiovascular toxicity.

Despite growing evidence, standardized protocols for evaluating MNP cardiotoxicity remain lacking, and human-based data are scarce. This review underscores the urgent need for long-term, mechanistic studies and regulatory frameworks to assess cardiovascular risks posed by environmental MNPs. Advancing this research frontier is critical to understanding the public health implications of chronic plastic particle exposure.

Graphical abstract

Introduction

Plastic is one of the most important goods in modern civilization [1–3]. It is a material with very lightweight, very long life, is cheap price, and contains many properties with wide applications worldwide [4, 5]. From bottle caps to dolls, cosmetics to electronics, and chocolate wrappers to food packages, the kingdom of plastic has spread everywhere [6, 7]. Most of these plastics are left in the environment without decomposition and are turned into smaller pieces due to environmental factors such as weathering or photodegradation [8, 9]. Pieces of plastic smaller than 5 mm are called micro- and nano-plastics (MNPs) [10, 11]. This term was first mentioned in 2004, and since then, many researchers have been interested in researching these particles [2]. MNPs are divided into two general groups, primary and secondary [12, 13]. Primary MPs are plastics that are produced in micro and nano sizes [8]. The secondary type is obtained from the fragmentation of large plastics into smaller pieces. MNPs are found in various forms such as spheres, fibers, irregular shapes, pellets, and fragments [14]. Research shows that MNPs have been found in Air, seas [15], beaches [16], deserts [17], snow [18], and rainwater [19], animal bodies [20, 21], and humans [22].

Ingestion, inhalation, and skin contact are among the main routes of human exposure to MNPs. The presence of MNPs in the human body has led to increasing concerns about health risks. Their presence in the human body has been reported in colectomy samples [23], saliva [24], lung tissue [25, 26], liver, kidney [27], breast milk, feces, urine, and human heart arteries [28]. Studies show that long-term contact with MNPs can have destructive effects on the functioning of the immune and hormonal systems, the thyroid gland, and the cardiovascular system, as well as causing oxidative stress and cell disorders [29–32]. However, human studies still require further work and a definitive determination of relevant health effects.

A wide range of studies on animal and human cell models show the effect of these MNPs on the cardiovascular system [33–35]. The term heart disease is usually used to refer to a heart attack, however, heart disease includes other heart diseases such as coronary artery disease, heart failure [36],, cardiac arrhythmia, and [37, 38]. Despite rapid advances in diagnosis and treatment, one-third of heart attack patients still die, and two-thirds of those who survive never fully recover and return to normal life [39]. These diseases impose a huge cost on the healthcare systems of the countries. However, cardiovascular diseases (CVDs) are one of the most preventable non-communicable diseases of humans. Nearly 18 million people died due to cardiovascular diseases in 2016 [40]. Factors such as smoking, drinking alcohol, diabetes, high blood pressure, and stress are risk factors for CVDs [41, 42]. But researchers also consider other factors to be involved, such as unhealthy diet, inactivity, and air pollution [43]. In addition, scientists are establishing a link between MNPs and cardiovascular risk factors. For example, studies have shown the effect of these particles on abnormal blood velocity [44], decreased cardiac output [45], altered heart rate (HR) [46], and Myocardial fibrosis [47], have reported.

These effects depend on the shape and size and structural characteristics, duration of exposure, and dose of exposure to MNPs [48]. Based on global statistics, more than 8 billion tons of plastic have been produced in the world since 1950. The problem is that the leap in plastic production is increasing every year and has now reached 400 million tons per year. This increasing growth is alarming.

In the last decade, plastic waste pollution has been twice as much as in the previous decade. Estimates show that this amount will increase to three times by 2060. According to these statistics, some harmful consequences may appear in the cardiovascular systems of humans and animals. In vitro and in vivo studies investigated the potential risks of MNPs for the cardiovascular system. However, there are gaps regarding the adverse effects of MNPs on the cardiovascular system and the behavior of these particles [49]. Therefore, it is necessary to systematically investigate the potential effects of MNPs on cardiovascular toxicity and CVDs in humans. This review provides a comprehensive overview of the problems caused by MNPs on cardiovascular toxicity.

Materials and methods

In this literature, on 04-03-2024, a search was made from PubMed, Scopus, and Web of Science databases with the following keywords. This systematic review was completed by the PRISMA statement [50] (Fig. 1).

Fig. 1.

PRISMA flow diagram

• PubMed: (“microplastic*“[Title/Abstract] OR “nanoplastic*“[Title/Abstract] OR “Microplastics“[MeSH Terms]) AND (“Cardiovascular system“[Title/Abstract] OR “Cardiovascular Diseases“[MeSH Terms] OR “Cardiotoxicity“[MeSH Terms] OR “Cardiovascular toxicity“[Title/Abstract] OR “Cardiovascular health“[Title/Abstract] OR “Heart“[Title/Abstract] OR “Heart“[MeSH Terms])

• Web of science: (TS=(microplstic* OR nanoplastic*)) AND (TS=(“ Cardiovascular system " OR " Cardiovascular Diseases *” OR " Cardiotoxicity " OR " Cardiovascular toxicity " OR " Cardiovascular health " OR " Heart “)).

• Scopus: TITLE-ABS-KEY (microplastic* OR nanoplastic*) AND TITLE-ABS-KEY (“Cardiovascular system " OR " Cardiovascular Diseases " OR " Cardiotoxicity " OR " Cardiovascular toxicity " OR " Cardiovascular health " OR " Heart “).

A total of 415 articles were initially retrieved from the mentioned databases. After removing 153 duplicate articles using software tools, the authors conducted a more detailed screening. This process led to the exclusion of 71 review articles, 12 editorial notes, comments, and letters, as well as non-English articles. Following the evaluation of titles and abstracts, 94 articles were deemed irrelevant as they focused on pollutants other than MNPs affecting the cardiac system or the effects of MNPs on organs other than the heart and blood vessels.

Inclusion criteria

• Peer-reviewed original studies published in English.

• Studies investigating the cardiovascular effects (e.g., cardiotoxicity, arrhythmia, blood pressure, myocardial damage) of microplastics and/or nanoplastics (MNPs).

• In vivo studies conducted on aquatic animals, terrestrial animals, or rodents.

• In vitro studies using human or mammalian cardiovascular-related cells (e.g., cardiomyocytes, endothelial cells).

• Studies that report dose, duration, and particle characteristics (size, type, concentration) of MNP exposure.

• Studies published between January 2000 and March 2024.

Exclusion criteria

• Review articles, meta-analyses, editorials, letters to the editor, and conference abstracts.

• Non-English publications.

• Studies focusing solely on non-cardiovascular outcomes (e.g., reproductive, hepatic, or neurological effects) without reporting cardiovascular endpoints.

• Articles evaluating plastic-associated chemicals (e.g., phthalates, BPA) without direct exposure to MNPs.

• Studies with unclear methodology, lacking adequate data on MNP characteristics or experimental design.

From the initial pool of 415 articles, after removing duplicates and irrelevant studies, 72 articles specifically addressing the impact of MNPs on the cardiovascular system were selected for review(Fig. 1). These studies were categorized as follows:

• In Vivo Studies on Aquatic Animals (43 studies):

  These studies primarily focused on the exposure of various aquatic species to MNPs. The findings indicated that MNPs can cause significant cardiovascular stress in these animals, leading to inflammation, oxidative stress, and tissue damage in the heart and blood vessels.

• In Vivo Studies on Mice (22 studies):

  Research on mice revealed that exposure to MNPs can result in increased blood pressure, atherosclerosis, and arrhythmias. The studies also showed that MNPs can induce oxidative stress and inflammation, which are critical factors in the development of cardiovascular diseases.

• In Vitro Studies on Human Cells (7 studies):

  These studies examined the effects of MNPs on cultured human cardiovascular cells. The results demonstrated that MNPs can cause cellular damage, oxidative stress, and inflammatory responses in heart cells, which may contribute to the development of cardiovascular diseases.

Overall, the review highlights the potential cardiovascular risks associated with MNPs exposure, emphasizing the need for further research to fully understand the mechanisms and long-term effects of MNPs on human health.

Results and discussion

Toxic effects of MPs on the cardiovascular system

MNPs pose significant risks to the cardiovascular system. Once they enter the bloodstream, these minute particles can reach the heart and blood vessels, leading to inflammation and tissue damage. Research indicates that MPs can contribute to higher blood pressure, the development of atherosclerosis, and irregular heart rhythms. Furthermore, MPs in the body can cause oxidative stress, harming heart cells and thereby elevating the likelihood of cardiovascular diseases.

Impact of MPs on aquatic animals and terrestrial animals’ heart rate

Alterations in heart rate, including both bradycardia and tachycardia, are among the earliest and most consistent physiological responses observed in aquatic species exposed to micro- and nanoplastics (MNPs) [51–56]. These effects are particularly evident in zebrafish (Danio rerio) models, where PS-NPs and MPs disrupt normal cardiac rhythms through multiple interconnected pathways (Table 1).

Table 1.

Impact of MPs on the cardiovascular of aquatic animals

Species	Type	Size	Dose	Duration	Impact	Ref
Zebrafish embryo	PE	-	25, 50, 100, 200 µg/ml	96 hpf	NOAEL is 50 µg/mL Severe pericardial edema Increase NOAEL: decrease CO, decrease blood flow velocity Decrease angiogenesis	[45]
Zebrafish	PS	700 nm	-	24 h	Accumulation in heart	[57]
Zebrafish (Danio rerio)	PS	10 nm	0.04, 34 ng L-1, and 34 µg L-1	144 h	Decrease HR	[52]
Zebrafish	Polylactic acid	5–50 μm	0.1, 1, 10, and 25 mg/L	90 days	Oxidative stress Myocyte damage	[58]
Zebrafish embryo	Polyacrylonitrile microfibers	60 μm	10 µg/L, 100 µg/L, 1 mg/L, and 10 mg/L	7 days	Increase HR Pericardial edema	[59]
Marine medaka (Oryzias melastigma)	PS	10 μm	2, 20, and 200 mg/L	60 days	Decrease HR of the offspring	[60]
Zebrafish embryo	PS	1 μm, 3 μm	0.01, 0.1, 1.0 and 10.0 mgL-1	72 h	Increase HR Phenotypic changes	[61]
D. magna	PS	2.0–2.9 μm	15 mg/L	Acute dietary exposure:72 h chronic dietary exposure:21days	Increase HR Induced oxidate stress	[62]
Cyprinus carpio (carp)	PS	1–10 μm	1000 ng/L	21 days	Myocardial tissue damage via the TLR4 \NF-κB pathway	[63]
Zebrafish	PS	42 nm	0.1, 1 and 10 mg/mL	5 days	Decreased HR	[64]
Zebrafish	PS	100 nm	(0, 100, 200, and 400 mg/L)	96 h	Decrease HR	[55]
Carp	PS	50 nm, 100 nm and 400 nm	1000 µg/L	28 days	Induced oxidative stress Induced inflammation and apoptosis	[65]
Zebrafish (Danio rerio)	PS, PCB	80 nm	PS (0.2 mg/L, 1 mg/L, 5 mg/L)- PCB (0.01 mg/L, 0.1 mg/L, 1 mg/L)	24 h	PCBs can seriously damage the bone and heart development of zebrafish, while the presence of NPs significantly enhanced the toxicity of PCBs in zebrafish	[66]
Zebrafish (Danio rerio)	PS	15 nm	50 mg/L-	96 h	Down-regulation in cardiac, vascular, and immunogenic pathways	[67]
Zebrafish embryo	PS	50 nm	1 mg/L	96 h	Decrease HR Decrease Bmp4 gene expression Decrease Gata4 gene expression Cardiac deformities	[68]
Zebrafish embryo	PS, PE	From 10 to 1000	From 2000–200,000 MP L− 1 to 12.5–100 mg L− 1	96 h	Decrease HR	[69]
Zebrafish	PE	0.5 μm	1, 10 and 100 µg/ml	96 hpf	Structural heart alternation Impaired cardiac function	[70]
Marine medaka, Oryzias melastigma	PS	50 nm	55 µg/L	21 days	Decreased embryonic HR	[71]
Zebrafish (Danio rerio)	PS	30 nm 50 nm 51 nm	30 and 50 mg/L	120 hpf	Decrease HR	[72]
Zebrafish	PS	0.2, 1.0, and 10 μm	20 µg/mL	-	Greater cardiotoxicity by small-size vs. large-size particles	[73]
Zebrafish	PS	10 μm	0.05, 0.1 mg/L 1, 5, 10 mg/L	8, 24, 32, 48 and 96 hpe (HPF)	Increase HR in zebrafish embryo and larvae	[56]
Zebrafish	PS	100 nm	250 items of µ-PS or 2 × 104 item of n-PS suspended in 50 mL exposure solution	72 hpf	Accelerated HR and blood flow velocity in the embryo	[44]
Zebrafish	PS	3–12 μm	10 mg/g dry food	21 days	Decline heart function DNA damage Induce oxidative stress	[74]
Tilapia (Oreochromis niloticus)	PP	-	100 and 500 µg/body weight	30 days	Increase cholesterol Increase heart mass	[75]
Zebrafish	PGA PBAT	3 μm	from 0.24 to 12.72 mg plastic/L	3 months	Heartbeat suppression Pericardial edema	[76]
Zebrafish (Danio rerio) embryo	PS	20–100 nm	0 (control), 0.1, 1, and 10 ppm PS NPs	114 h	No change in pericardial area Decrease HR Accumulation in pericardium	[77]
Zebrafish (Danio rerio) Embryo	PS, PHE	80 nm	5 mg/L PS, 10 mg/L PS, 0.1 mg/L PHE, 0.2 mg/L PHE, 5 mg/L PS + 0.1 mg/L PHE, 5 mg/L PS + 0.2 mg/L PHE	-	Pericardial edema Increase HR	[78]
Daphnia magna	PS	154.1 ± 2.9 nm	5 µg/L	Lifelong	Decrease HR	[79]
Goldfish Carassius auratus Larvae	PS	70 nm and 5 μm	10, 100 and 1000 µg/L	1, 3, and 7 days	Increase HR Elevated ROS level	[46]
Zebrafish embryo	PS	50 nm	5.0 mg/L	72 h	Pericardial edema	[80]
Zebrafish embryo	PET	Particles (150 μm) Fibers (3–5 mm in length and 20 μm in diameter)	0.5gr/100 ml	72 h	Increase HR	[81]
Lates calcarifer	PS	1 μm	0.5 µg and 1 µg/ml	48 h	Heart tissue damage	[82]
Tadpoles	PS	10 μm	125–1250 mg/L	12 h	Accumulation in heart tissue	[83]
Zebrafish embryo	PS	80 nm	50 µg/L, 100 µg/L, 1 mg/L, 5 mg/L, 10 mg/L	120 h	No significant change in HR Pericardial edema Accumulation in heart tissue	[84]
Zebrafish embryo	PET	5 mm	0.5, 1, 5, 10 and 20 mg/L)	144 h	Increase HR	[85]
Oryzias melastigma embryo	PVC	53–106 μm	1 × 106 particles/L	25 days	Pericardial edema Changing in the phenotype of the heart Up-regulation of the cardiac development genes (GATA4 and NKX2.5) Increase HR	[86]
Zebrafish	PE	200 nm	Embryo (10 mg/L) Adult (2 mg/L)	Embryo (120 hpf) Adult (7days)	Accumulation in the heart of larvae but not adult	[87]
Daphnia magna	PE	20 nm	1 mg/L 50 mg/L	-	Decrease HR	[88]
Mytilus galloprovincialis	PS	14–20 μm	10 mg/ml	96 h	Increase HR	[89]
Zebrafish	PE, PE, PP, PS	52–74 μm	Embryo: 102, 103, 104, 106 particles/L Larvae: 102, 104 particles/L	Acute toxicity test: 4 h to 5 days Chronic toxicity test: 10 days to 28 days	Embryo: no impact on development at 102 particles/L; accelerated heartbeat and increased death at 104 and 106 particles/L for PE, and PS Larvae: No impact on feeding, growth, or oxidative stress; locomotion and AChE activity inhibited by MNPs at 104 particles/L	[90]
Daphnia magna	PE	32–38 μm	0, 5, 40, and 160 mg/L	1, 3, and 5 h	Decrease HR	[54]
Zebrafish	PS	20 nm	3nl	4 h	Increase HR in offspring Increase blood flow rate in offspring	[91]
Medaka	PS	10 μm	20 and 200 µg/L			[92]
Medaka	PS	0.05, 0.50 and 6.00 μm	0.1, 1 × 103,and 1 × 106 particles/mL	4 hpf	Heart rates significantly increased from 3 to 4 days post-fertilization Heart rates decreased from 8 to 9 days of post-fertilization underexposure Dose dependent effect: 0.1 particles/mL: Initial increase followed by a decrease in heart rates 1 × 10^3 particles/mL: Consistently stronger heart rates from 3 to 9 days of post fertilization 1 × 10^6 particles/mL: Significant decrease in heart rates	[93]

Bradycardia and depressed cardiac output

Exposure to PS-NPs has been shown to induce bradycardia, suggesting interference with cardiac pacemaking and autonomic regulation. Several mechanisms contribute to this effect:

• Neurotoxicity:

  Decreased spontaneous contraction frequency and impaired neural regulation of cardiac tissue have been reported, indicating that PS-NPs may interfere with cholinergic or adrenergic signaling pathways [52].

• Oxidative Stress:

  Elevated levels of malondialdehyde (MDA) and decreased antioxidant enzyme activity (e.g., SOD, GPx) suggest that redox imbalance impairs mitochondrial function, leading to slower cardiac activity and reduced perfusion [60].

• Histological Damage:

  PS-NPs have been shown to cause histological damage in various tissues, including gills, liver, and gonads. Notably, damage to the gills could affect oxygen uptake, which may, in turn, impact heart rate. Structural changes in these organs can disrupt overall physiological balance, including cardiac function [60].

• Endocrine Disruption:

  The study also indicates that PS-NPs disrupt the reproductive endocrine system in a sex-dependent manner. While the primary focus was on reproductive effects, endocrine disruptions can have broader physiological impacts, including on heart rate. Alterations in hormonal balance can influence cardiovascular function, as sex hormones are involved in regulating heart rate and other processes [60].

Tachycardia and other alterations induced by MPs

The research reveals that exposure to MPs leads to notable alterations in heart rate among zebrafish larvae. At higher concentrations, MPs can accelerate the heart rate, deviating from normal developmental patterns. This change, coupled with pericardial edema (fluid accumulation around the heart), suggests that MPs may induce physiological stress, possibly due to inflammatory responses or direct interference with cardiac tissue [59, 61]. The mechanisms behind this tachycardia include:

• Reactive oxygen species (ROS) and oxidative stress:

  Increased ROS levels and mitochondrial quantity in larvae exposed to MPs indicate heightened oxidative stress. This stress can disrupt cellular and tissue functions, including those of the heart, potentially leading to abnormal heart rate patterns [59, 61].

• Signal transduction pathways:

  MPs affect lipid metabolism and calcium ion signaling pathways, which are crucial for normal cardiac function. Disruptions in these pathways can alter how signals are transmitted and processed within the heart, impacting heart rate [59].

• Antioxidant response:

  In response to PS-MP exposure, the antioxidant system adapts, showing increased activity of the superoxide dismutase (SOD) enzyme. This may serve as a compensatory mechanism to counteract oxidative stress. However, the balance between ROS and antioxidant activity, including enzymes like SOD and glutathione peroxidase (GPx), can vary with concentration and particle size, influencing overall heart rate effects [61].

• Micromitophagy and apoptosis:

• High concentrations of MPs trigger micromitophagy and apoptosis in intestinal epithelial cells via the Kras/MAPK signaling pathway. Although the primary focus was on the intestines, these cellular processes could have systemic effects, including on cardiac function [59, 61].

Overall, the data suggest that both PS-NPs and MPs can significantly disrupt normal cardiac function in aquatic organisms, with various mechanisms contributing to observed changes in heart rate. As depicted in Fig. 2, ROS-mediated oxidative stress and NF-κB-driven inflammation are central mechanisms in MNP-induced cardiovascular damage.

Fig. 2.

Mechanistic pathways of MNP-Induced cardiotoxicity

Impact of MPs on aquatic animals and terrestrial animals’ edema

Now, let’s discuss the potential efficacy of MNPs in inducing pericardial edema. The pericardium is an important structure surrounding the heart. Its primary function is to secrete serous fluid, which facilitates cardiac function. Pathological conditions can cause excessive fluid to flow into the pericardial cavity, resulting in pericardial edema. More fluid in the pericardial region can exert pressure on the heart and impact its function. Some of the pathological disorders that can induce pericardial edema include bacterial, fungal, and viral infections; other causes include chest trauma, inflammatory diseases, and heart failure. However, environmental factors are one of the most prominent causes of pericardial edema, particularly in animal species [94, 95]. MNPs, a global concern today, present significant environmental and health risks due to their ability to infiltrate the body, penetrate tissue barriers, and move through the bloodstream to reach other organs. They can put more stress on cells and cause inflammatory responses, damaging vascular endothelial cells and letting fluid leak into the tissues and pericardial cavity. Leakage and fluid accumulation around the heart cause pericardial edema [76].

Zebrafish embryos are one species used to study the influence of MNPs. Studies suggested that MNPs accumulate in the yolk sac within 24 hpf and move to the heart across development, causing pericardial edema and a decrease in heart rate [96].

A study conducted by SUN et al. indicated that exposing embryo zebrafish to different concentrations of polyethylene NPs at specific concentrations of 100 and 200 µg/ml caused pericardial edema and yolk sac degeneration. Despite the presence of pericardial edema and yolk sac disintegration, there was no change in heart rate, which can be explained by the fact that different factors might influence heart rate. Based on this experiment, no detrimental consequences were observed at a concentration of 50 µg/mL [96]. Another study by Zhang et al. also demonstrated that pericardial edema was observed in zebrafish larvae exposed to 100 µg/ml, 1, and 10 mg/l of polyacrylonitrile microfibers [59]. Both studies indicate a trend that depends on the dose.

It’s important to know that MNPs can absorb harmful environmental chemicals and release them into biological systems. The chorionic membrane in zebrafish serves as a protective barrier against contaminants, hence influencing the level of toxicity experienced by the embryo. There are pores in them that exchange oxygen and nutrients. If MNPs can’t pass through these pores, they stick to the cell membrane and it should be noted that the buildup of chemicals in an organism impacts its level of toxicity [97, 98].

Since the heart is the first organ to develop and function in fish, its development is particularly susceptible to chemical pollutants, resulting in pericardial edema [99]. Based on the Wang et al. study, exposure to various doses of polystyrene could cause pericardial edema, which is an important indicator of cardiotoxicity in this animal species. This study stated that doses lower than 50 µg/L failed to cause adverse cardiac effects directly [84]. Researchers conducted another study to investigate the impacts of phenanthrene and polystyrene nanoplastics on zebrafish embryos. The findings revealed that while both of these pollutants were capable of inducing cardiac edema, polystyrene had a more significant impact on the occurrence of this disorder [100].

In this regard, other studies showed that microplastics (PS), PMP (primary MP), and SMP (secondary MP) derived from PVC could enter the yolk sac and damage the zebrafish embryo’s heart, leading to pericardial edema [55, 101].

Our systematic review provided further depth to our understanding of the relationships between the impact of MNPs on pericardial edema.

Impact of MPs on aquatic animals and terrestrial animals’ fibrosis

MPs pollution is an emerging environmental problem that not only causes environmental pollution but also makes a vast threat to living organisms. Because of their high distribution and complicated effects on living organisms. A summary of the collected studies is given in Tables 1, 2 and 3.

Table 2.

Impact of MPs on the cardiovascular of terrestrial animals

Species	Type	Size	Dose	Duration	Impact	Ref
Mouse	PET	5–10 μm	0.5, 5, and 50 µg/mL	90 days	Cardiomyocyte destruction and fibrosis	[102]
Pig(Pietrain x Duroc)	PET	Average size 153.09 μm	0.1 g/pig/day 1 g/pig/day	4 weeks	Increase the prevalence of heart diseases	[103]
Mouse	PE	10–45 μm	0, 6, and 60 µg	Gestational day 9 to postnatal day (PND) 7	Increase cardiac mass	[104]
Mice	PS	100 nm	10–100 µg/mL	30 and 180 days	Increase vascular accident incidence	[105]
Rats	PS	0.5 mm	0.5, 5 and 50 mg/L	90 days	Elevated cTnI level	[106]
Mice	PS	(0.5 μm and 5 μm)	(0.1 µg/ml and 1 µg/ml)	12 weeks	Increase cardiovascular events incidence	[107]
Mice	PS	0.5 μm MP1 and 5 μm MP2	5 g/L	8 weeks	Induced inflammation Structural heart damage	[108]
Mice	PS	0.7918 ± 0.00273 μm	30 mg/kg	35 days	Accumulation of MNPs in heart	[109]
Mice	PS	300 nm	1 mg/kg	35 days	Structural heart alternation	[110]
Chicken	PS	5 μm	1 mg/L 10 mg/L 100 mg/L	42 days	Induced inflammation ATP production pathway disruption	[111]
Mice	PS	-	5 µg/g	2 weeks	Induced oxidative stress TGF-β1/Smad pathway activation Collagen accumulation	[112]
Chick	PS	5 μm	10 mg/L and 100 mg/L	42 days	Down-regulation of TnnT2, Nkx2-5, Gata4, TBX5 and ACTN2 Up-regulation of Endoplasmic Reticulum (ER) stress markers GRP78, PERK, eIF2α, IRE1, ATF4, ATF6 and CHOP	[113]
ApoE(-/-) Mice	PS	50 nm	2.5–250 mg kg(−1)	19 weeks	Increase total cholesterol in foam cells Up-regulation of MARCO gene/protein expression Exacerbated the artery stiffness and promoted the formation of atherosclerotic plaque	[114]
Wistar Rat	PS	0.5 mm	0.5, 5, and 50 mg/L	90 days	Elevated Creatine kinase-MB and cardiac troponinI Increase MDA Increase SOD, GPx, and CAT Up-regulation of interleukin (IL)−1β, IL-18 Up-regulation of Nfkb Activation of NLRP3 Activation of NLRP3 Inhibition of Caspase-1-dependent signaling pathway Morphological changes in cardiac tissue	[47]
Male Wistar Rats	PET	160 μm	1.4, 35, or 125 mg/kg	24 h	Elevated TG level	[115]
Mice	PS	-	10%, 1%, and 0.1% by weight of the feed	42 days	Decrease heart mass index	[116]
Mice	PET	5–10 μm	5–50 µg/mL	90 days	Capillary congestion Myocardial fiber breakage and fibrosis	[117]
C57BL/6 Mice	PS	10 μm	1000 µg/L	6 months	Intramyocardial lipid deposition Disruption of myocardial arrangement Nuclear swelling Enhanced dissolution Inflammatory damage Severe cardiac fibrosis Elevated CK-MB and LDH Elevated AST level (marker of myocardial infarction and myocarditis) Elevated cTnI level Elevated TC, TG, and LDL-C levels Decrease HDL-C level Increase chronic cardiotoxicity	[118]
C57BL/6 Mice	PET	5 μm	1000 µg/L	180 days	Induced oxidative stress and hyperlipidemia Aggravated vascular lesions Cardiac tissue structure damage Lipid and collagen deposition in heart Elevated AST and CK levels Differentially expressed genes in the mouse aorta	[119]
Pregnant Rats	PS	20 nm	8.8 × 1014 particles/mL; 10 mg/mL	24 h	Increase in gross maternal heart weight Increase aortic vascular smooth muscle responsivity Impaired endothelial function Increase aorta mean velocity Increase LVOT mean velocity Increase LVOT mean pressure gradient Increase LVOT stroke distance	[120]
Mice	PS	1–100 nm	3 mg/kg 6 mg/kg 10 mg/kg	8 weeks	Significant cardiac aging Induced oxidative stress Significant inflammatory damage	[121]
Frog	PE	-	60 mg/L	168 h	No significant differences in heart rates No cardiotoxicity	[122]
Chicken	PS	25 nm	5 mg/ml, 1 mg/ml, 0.1 mg/ml, 0.01 mg/ml.	24 h, 4 days, and 8 days	Congenital heart defects Impaired cardiac function	[123]
Mice	PS	10 μm	Mice were exposed to MPs in drinking water at a concentration of 1000 g/L	180 days	Induced myocyte apoptosis	[124]
Mice	PS	40 nm	0 µg/day, 16 µg/day, 40 µg/day, and 100 µg/day.	1 week, 4 weeks, and 12 weeks	Dose-dependent and time-dependent cardiac injury Oxidative stress and inflammation Heart structural damage	[125]
Mice	PS	1 μm	25 µg 50 µg	4 weeks	Structural heart alternation	[126]

Table 3.

Impact of MPs on the cardiovascular of human cells

Cell model	Type	Size	Dose	Duration	Impact	Ref
Neonatal rat ventricular myocytes (NRVMs)	PS	-	-	60 min	Decrease intracellular Ca Impaired electrophysiological activity Impaired myocardial contractility	[127]
Chicken embryo cardiomyocytes	PS	5 μm	0.5 mg/mL	24 h	Down-regulation of LC3, ATG5, Beclin1 and P62 and P53 (autophagy-related genes)	[113]
Porcine coronary artery endothelial cell	PS	20 nm	0.1, 1, and 10 µg/mL	24 h	Endothelial dysfunction Oxidative stress Up-regulation of NADPH oxidases gene Elevated P53, P21, P22, P16, and NOX protein levels	[128]
Human ESC lines H1	PS	-	5 µg/mL, 20 µg/mL	24 h and 48 h	Induced cell injury and apoptosis in hESCs (dose- and time-dependent) Mitochondrial damage Elevated Cyt-c, Bax and Caspase-3 levels Decrease Bcl-2 level Induced apoptosis	[129]
H9C2 cells	PET	5–10 μm	5–50 µg/mL	90 days	Induced oxidative stress Cardiomyocyte apoptosis Myocardial fibrosis	[117]
H9c2 and AC16	PS	1–100 nm	0, 0.1, 0.25, 0.5, 0.75, 1.0, 2.0 and 5.0 mg/mL	60 min	Induced cardiomyocyte senescence	[121]
Human pluripotent stem cell-derived three-dimensional cardiac organoid (CO) model	PS	1 μm	0.025 µg/mL, 0.25 µg/mL, and 2.5 µg/mL	72 h	Induced oxidative stress, inflammation, and apoptosis Collagen accumulation Cardiac dysfunction and hypertrophy	[126]

Although, current studies mostly focus on the biogenic risks of MPs to aquatic organisms, there is an urgent need to provide a review of studies related to health risks to terrestrials such as mammals.

MPs are potential threat to both terrestrial and marine ecosystems by directly affecting the organs and activating a plethora of intracellular signaling, that may lead to cell death. There is accumulating evidence that supports the serious toxicity caused by MPs at all levels of biological complexities (biomolecules, organelles, cells, tissues, organs, and organ systems) and the involvement of the reactive oxygen species (ROS) in this process [130, 131]. Intracellular ROS production by MPs have been shown by multiple groups using various model systems [130, 131].

Formation of ROS is the molecular initiating event, leading to oxidative stress and inflammation [131].

MPs in the environment can be ingested by organisms through the food chain, and can cause many toxic effects on different organs of the body including cardiovascular system [132]. Cardiotoxicity is one the main toxic effects of MPs in the body [133].

MPs could accumulate in cardiomyocytes of rats and induce cardiac tissue damage and apoptosis of myocardial cells. there are relatively few studies on the cardiotoxicity caused by MPs, which can be used as directions in future research [47].

In mammals, reported studies showed impaired heart contractility, neonatal cardiomyocyte apoptosis, and activation of fibrotic processes [134].

As a consequence of oxidative stress caused by the MPs, different types of organ damage are observed in living species, such as cardiotoxicity, pulmonary toxicity, etc.

A study published by Wang et al. also demonstrated the role of MP-induced mitochondrial depolarization in the enhancement of cellular oxidative stress in Caco-2 cells. Another study by Florance et al. revealed that MPs promote lipid accumulation in macrophages, which eventually leads to a decrease in MMP and increased oxidative stress [135, 136].

mitochondria serve as a major target for the MPs to induce oxidative stress in cells and tissues, by modulating a wide array of downstream signaling cascades [130].

The MPs also measurably induced pro-inflammatory cytokines IL-6 and TNF-α.

Lu et al. investigate the toxic effects of PET MPs on ICR mice and H9C2 cells by different treatment groups. The results indicated the cardiac tissue of mice in the PET-H (50 µg/mL) group showed significant capillary congestion, myocardial fiber breakage, and even significant fibrosis compared to the PET-C (control) group (P < 0.01). Results of the TUNEL assay demonstrated significant apoptosis in myocardial tissue in the PET-H and PET-M (5 µg/mL) groups (P < 0.01) [117].

Another study published by Zhang et al. invested the induction of myocardial inflammation and cell death via the TLR4/NF-κB pathway in carp. In this study they showed that PS-MPs exposure could induce inflammation, apoptosis, and necrosis in carp myocardial tissue and cardiomyocytes [63].

Zhang et al. in 2022, also published a study which showed PS-MPs exposure triggered oxidative stress and ROS overload in myocardium. Detailed mechanistic investigation indicated that PS-MPs triggered pyroptosis via NF-κB-NLRP3-GSDMD axis and exacerbated myocardial inflammation (NLRP3, Caspase-1, IL-1β, IL-18, ASC, GSDMD, NF-κB, COX-2, iNOS and IL-6 overexpression). Additionally, PS-MPs induced mitochondrial damage (TFAM, OPA1, MFN1 and MFN2 down-expression, DRP1 and Fis1 overexpression) and energy metabolism disorders (HK2, PKM2, PDHX and LDH up-regulation) by inhibiting AMPK-PGC-1α pathway [111].

Zhou et al. in 2023 showed that Low-dose of polystyrene MPs induce cardiotoxicity in mice and human-originated cardiac organoids [126].

Yang et al. in 2020 showed that MPs at higher concentrations can cause damage to fish larvae and MPs are potentially more hazardous [46].

A study investigated in October 2020, indicated that Polystyrene MNPs cause cardiac fibrosis by activating Wnt/β-catenin signaling pathway and promoting cardiomyocyte apoptosis in rats. The results showed that polystyrene MNPs could cause cardiac fibrosis and dysfunction, induce oxidative stress and apoptosis [106].

Hemodynamic dysregulation and pro-thrombotic effects of MNPs

Beyond direct cardiomyocyte toxicity, emerging evidence suggests that micro- and nanoplastics (MNPs) profoundly affect systemic cardiovascular physiology. Critical pathways include dysregulation of blood pressure, endothelial barrier impairment, vascular smooth muscle dysfunction, and thrombogenesis. These effects are increasingly recognized as central to the cardiovascular burden of MNPs, expanding the focus from myocardial injury to whole-organism vascular health.

Vascular tone and blood pressure alterations

The vascular system appears to be a primary and highly sensitive target of MNP exposure. In vitro and in vivo studies demonstrate that MNPs interfere with vascular tone regulation through multiple converging mechanisms:

Nitric oxide (NO) bioavailability

Several endothelial cell models have shown that exposure to polystyrene nanoplastics (PS-NPs) suppresses endothelial nitric oxide synthase (eNOS) activity and reduces NO production, a key mediator of vasodilation and vascular homeostasis. Reduced NO levels impair endothelium-dependent relaxation, favoring vasoconstriction and elevated blood pressure.

Oxidative stress and endothelial senescence

MNP exposure increases intracellular ROS generation and NADPH oxidase activation, which not only promotes vascular oxidative stress but also accelerates endothelial senescence. Senescent endothelial cells lose their ability to regulate vascular tone, further contributing to arterial stiffness and impaired vasodilation.

Microvascular leakage and barrier dysfunction

Evidence from zebrafish and rodent models indicates that MNPs compromise endothelial barrier integrity, causing microvascular leakage and impaired microcirculatory perfusion. These alterations may lead to tissue hypoxia and hemodynamic instability.

Hemodynamic load and vascular smooth muscle reactivity

In rodent models, exposure to PS-NPs has been linked to increased aortic mean velocity, elevated left ventricular outflow tract (LVOT) pressure gradients, and enhanced stroke distance. These changes suggest that MNPs alter vascular smooth muscle contractility and systemic resistance, imposing a higher hemodynamic load on the heart.

Taken together, these findings indicate that endothelial dysfunction and vascular dysregulation are not secondary phenomena but rather pivotal mechanisms of MNP-induced cardiovascular toxicity. Persistent vascular injury may contribute to hypertension, microvascular ischemia, and increased susceptibility to long-term cardiovascular disease [137].

Endothelial dysfunction via redox imbalance

In vitro analysis of porcine coronary endothelial cells showed that exposure to PS-NPs induces endothelial senescence and eNOS downregulation, accompanied by increased ROS production and enhanced NADPH oxidase expression [138]. These changes impair nitric oxide (NO) bioavailability, crucial for vasodilation and blood pressure regulation [128]. Importantly, antioxidant treatment with N‑acetylcysteine (NAC) or apocynin reversed both oxidative and senescence markers, highlighting a redox-sensitive mechanism.

Thrombogenesis and platelet activation

Polystyrene nanoplastics have been shown to enhance platelet aggregation in vitro and in vivo, with severity depending on particle size and surface chemistry [139]. For instance, amine-modified PS‑NPs (50 nm) strongly activate platelets via αIIbβ3 integrin-mediated mechanisms, both through direct membrane interaction and bridging adjacent platelets [140].

Moreover, PS-NPs can adsorb coagulation proteins such as factor XII and plasminogen activator inhibitor‑1, promoting thrombus formation in vivo.

A hamster model further confirmed that positively charged PS‑NPs cross the pulmonary capillary barrier and significantly increase thrombosis at blood concentrations of ≥ 50 µg/kg, while neutral or negatively charged particles had minimal effects.

These findings collectively suggest that MNPs may contribute to hypertension, endothelial activation, and thrombotic events, expanding the implications of plastic exposure from cellular to whole-organism cardiovascular dysfunction [128].

MPs impact on cardiovascular in human cells

Herein, we will talk about how MNPs affect different cells, such as H9C2, AC16, H1 derived from ESC, Neonatal rat ventricular myocytes, Chicken embryos cardiomyocytes, porcine endothelial cells, and RAW264.7 [113, 114, 117, 121, 127–129].

First of all, when it comes to the impact of MNPs on cells, the main question that crosses the mind is how MNPs internalize and entire the cells. Studies reported that NPs were able to transfer into different cells according to dose and time-dependent manner, however, the precise mechanism is also uncertain [121, 129]. As a result, they have a tremendous impact on cell function and shape by altering gene expression, enhancing oxidative stress and inflammation, mitochondrial disruption, and subsequent apoptosis. Furthermore, high serum concentration in culture media was considered an effective way to avoid particle penetration [128].

In terms of oxidative stress and inflammation, numerous studies have figured out that MNPs can induce oxidative stress contributing to senescence. MNPs can accomplish this in a variety of ways, Firstly, Substantial decrease in antioxidant enzymes, like SOD, catalase, and GSH. Secondly, promoting peroxidation and ROS production. To prove this, lots of evaluations were done that revealed a significant increase in TNFα, IL-1β, IL6, IL8, NF-κB, Hmox1, Ngo1, and Nrf2 levels [117, 121, 126, 129]. whereas, observations showed that pretreatment with N-Acetyl-L-cysteine (NAC) resulted in a relative decrease in oxidative stress after MNP exposure [117].

It has been believed that aging is an unstoppable process that occurs in cells second by second. Cardiac aging is the most common cause of death among elderly people. MNPs can make room to facilitate this process. Studies have demonstrated an upregulation in p53, p16, and p21 expression indicating the aging process acceleration. Further evaluation also revealed the propagation of Sa-β-gal expression, a prominent senescence marker. Taken together, these findings suggest that cells exposed to MNPs experience cell cycle arrest [121, 128]. Moreover, utilizing neferine, NF-κB inhibitor, alleviated MNPs-induced senescence [121].

It is interesting to note that mitochondria play a substantial role in cardiac cells due to their high demand for ATP. MNPs disrupt mitochondrial function through the following descriptions: Excessive calcium influx into mitochondria, decline in oxygen consumption rate (OCR) and ATP production, and decreased mitochondrial membrane potential, following these events, cytochrome-C (Cyt-c) is released into the cytoplasm, Bax expression is promoted and Bcl-2 and Caspase3 are decreased, All these together cause activation of the mitochondria-mediated apoptotic pathway [117, 121, 126, 127, 129].

Another debatable issue is how MNPs affect calcium metabolism in cells [126]. It was already said that the influx of calcium from the sarcoplasmic reticulum into the cytoplasm can cause mitochondrial dysfunction and ultimately cell death. Treating cells with the inositol 1, 4, and 5-trisphosphate receptor (IP3R) inhibitor (2-APB) was able to attenuate mitochondrial damage and augment cell viability [121]. In addition, MNPs can interfere with intracellular calcium homeostasis and consequently impair the contractility of cardiomyocytes [127, 129].

Interestingly, PS-MPs significantly correlate with concentration, inducing myocardial dysplasia. The myocardial dysplasia in chicken embryo cardiomyocytes was observed through 3 pathways. The first pathway involved the downregulation of TnnT2, Nkx2-5, Gata4, TBX5, and ACTN2. Another is to increase endoplasmic reticulum (ER) stress markers such as GRP78, PERK, eIF2α, IRE1, ATF4, ATF6, and CHOP expression, and the last is Deactivation of autophagy-induced genes LC3, ATG5, Beclin1 and P62. Furthermore, the addition of 4 PB illustrated the reversibility of all the above mechanisms [6].

While pathways such as NLRP3 inflammasome activation, Wnt/β-catenin signaling, and cGAS-STING activation have been proposed, few studies have utilized genetically modified or knock-out models to confirm causality. Future investigations employing transgenic animals or CRISPR-mediated knockdowns are critical to validate these mechanisms and identify therapeutic targets.

Factors affecting the accumulation of MPs in the circulatory system

MNPs particles of different sizes can enter the body in different ways. Smaller particles are easily absorbed through the respiratory and digestive systems and can enter the bloodstream. These particles can then be transported to various organs, including the heart. Studies have shown that MNPs particles with sizes less than 10 micrometers can easily pass through biological barriers and penetrate into heart tissues.

The entry of MNPs into the heart can have negative effects on cardiovascular health. These particles may cause inflammation and damage to heart cells and affect heart function. Also, MNPs can act as carriers of harmful chemicals and transfer these substances to heart tissues.

In general, the size of MNPs plays an important role in their ability to penetrate biological systems and cause negative health effects.

Studies show that the size and dose of MNPs can affect the severity of cardiovascular diseases. For example, in one study, MNPs were detected in more than 50% of fatty deposits in arteries, and a correlation between the level of MNPs and the severity of cardiovascular diseases was observed¹². Also, the presence of MNPs in plaques blocking blood vessels in the neck increases the risk of heart attack and stroke.

When injected at the blastula stage, polystyrene nanoparticles (PS-NPs) accumulated around the heart region and within the bloodstream at three days post-injection (dpi) [44, 77]. In contrast, no PS-NPs were observed in the ducts of Cuvier when injected at a later developmental stage. This indicates that the bioaccumulation and distribution of MNPs in the circulatory system are dependent on the particle sizes of MNPs [77].

For instance, when zebrafish embryos and larvae were separately exposed to PS-NPs (100 nm) and polystyrene microparticles (PS-MPs) (157 ± 52 μm), only the PS-NPs migrated through the bloodstream and reached the heart at 48–120 h post-fertilization (hpf) [141]. Similarly, PS-NPs (34.5 ± 10.8 nm) were first detected accumulating in the yolk sac as early as 24 hpf, and then in the pericardium by 48 hpf.

A recent study on Atlantic horse mackerel (Trachurus trachurus) living in a realistic environment reported an accumulation of MPs in internal organs such as the gills, heart, kidneys, and digestive system. Some MPs were retained in the circulation due to mechanical blockage in the capillaries [141]. MPs detected in the heart and its luminal blood were significantly smaller than those in other organs. The average diameter of suspected MPs in the cut organs in the gills was about 11 μm, in the heart 6.8 μm, and the digestive system 26 μm. Interestingly, MPs in the heart were of the same size range as hematocytes, corroborating the role of the circulatory system in the distribution of MNPs [141].

Besides fish, the movement of MNP to the heart via the circulatory system has also been observed in rodents [142]. For example, oral exposure of Wistar rats to PS-NPs (0.5 μm) for 90 days led to the presence of NPs in the myocardial cells at doses of 5 and 50 mg/L [142]. Similarly, after a 30 mg/kg body weight (BW) PS-NP treatment (0.79 μm) for 35 days, orally exposed mice exhibited prominent PS-NP accumulation in the blood, followed by blood-rich organs such as the spleen, lungs, kidneys, liver, small intestine, and heart. Similar findings have also been reported in C57BL/6 J mice, where PS-MNPs accumulated in the spleen, kidneys, heart, liver, lungs, and blood in a size-dependent manner after oral exposure to PS-MNPs (50–5,000 nm; 125–500 mg/kg BW) for 24 h [143].

The wide biodistribution of MNPs in various organs could be due to epithelial cell apoptosis and reactive oxygen species (ROS)-mediated intestinal barrier dysfunction caused by MNPs, which promoted MNP absorption and biodistribution. The passage of MNPs from the environment to the heart is influenced not only by particle size but also by surface modification. In a rodent study, amine-PS-NPs (60 nm) crossed the pulmonary blood barrier and caused thrombosis and pulmonary inflammation in hamsters. Additionally, when Fischer 344 rats were orally exposed to three differently charged (neutrally, positively, and negatively) PS-NPs (50 nm) for six hours, higher bioaccumulation of negatively charged PS-NPs was observed in the heart compared to those with neutral or positive charges [35, 144].

Overall, MNPs can penetrate the intestinal epithelium or pulmonary blood barrier, enter the bloodstream through the portal vein, redistribute in the blood, and then accumulate around the heart. MNPs larger than 0.5 mm are less likely to pass through the intestinal epithelium, and MNPs larger than 400 nm cannot penetrate the pulmonary blood barrier. When larger than 150 μm–10 μm in diameter, MPs cannot be absorbed into the blood or penetrate blood vessels, respectively. Subsequently, MNPs are distributed in internal organs with blood flow in a size-dependent manner, where smaller particles exhibit greater biodistribution [144].

Looking at Fig. 3, we can see that Severe Toxicity is most pronounced in the smallest size range (1–50 nm), with a count close to 12. Moderate Toxicity is Distributed across all sizes, peaking in the 100–500 nm range. Low Toxicity is Present across various sizes, highest in the > 10 μm category. This graph suggests that smaller MNPs are more likely to cause severe cardiotoxic effects.

Fig. 3.

Size-dependent graph of cardiotoxic effects of MNPs based on Tables 1 and 2

Emerging human evidence of MNP-associated cardiovascular risk

Although most of the existing data on MNP-induced cardiotoxicity is derived from in vivo and in vitro experimental models, recent human studies have begun to reveal compelling links between MNP presence and cardiovascular disease outcomes.

A pivotal study reported the presence of microplastic particles in more than 50% of carotid atherosclerotic plaques excised from patients undergoing endarterectomy. Notably, patients with detectable plastic particles in plaques had higher rates of past myocardial infarction and cerebrovascular events, suggesting that MNPs may contribute to plaque instability and thrombotic risk [145].

Similarly, demonstrated elevated levels of circulating polystyrene nanoplastics in patients with coronary artery disease (CAD) compared to healthy controls. These findings correlated with elevated biomarkers of endothelial dysfunction (e.g., ICAM-1, VCAM-1) and pro-thrombotic cytokines [146].

Furthermore, a cross-sectional environmental cohort study in urban China identified a positive association between airborne MNP exposure and blood pressure elevation, raising the possibility that inhaled particles may influence vascular tone and autonomic regulation.

These early findings suggest that MNPs are not just laboratory hazards but plausible contributors to human cardiovascular morbidity. Although causality has yet to be definitively established, the translational relevance of experimental models is strongly supported by these real-world observations.

Potential interventions and therapeutic strategies

Given the central role of oxidative stress, inflammation, endothelial dysfunction, and coagulation disturbances in MNP-induced cardiotoxicity, several therapeutic strategies have emerged based on experimental evidence:

Antioxidant therapy (NAC, Resveratrol, Apocynin, CoQ10)

N-acetylcysteine (NAC) is shown to significantly attenuate ROS production and restore NO bioavailability and eNOS activity in endothelial models and in vivo assays—indicating its potential to counteract MNP-induced redox imbalance [147].

Resveratrol, a polyphenolic antioxidant, demonstrated reduced expression of inflammatory markers (IL-8, VCAM-1, ICAM-1) and improved endothelial function in human clinical studies, supporting its potential for in vivo cardioprotection [148].

Apocynin, a NADPH oxidase (NOX) inhibitor, effectively reduced ROS and increased NO levels in endothelial (HUVEC) and hypertensive rat models, improving vascular reactivity [149].

Notably, NAC and apocynin represent promising agents to mitigate MNP-driven endothelial injury.

Coenzyme Q10 (CoQ10), though not yet directly tested against MNPs, has robust cardioprotective effects (via antioxidant and mitochondrial support) in heart disease, and could be explored in MNP contexts [150, 151].

ER stress modulation and autophagy restoration

In models of embryonic cardiomyocyte exposure to PS-MPs, treatment with 4-phenylbutyric acid (4-PBA) successfully reversed ER stress marker upregulation and restored autophagy balance, leading to improved cell morphology and gene expression. This highlights ER stress inhibition as a potential therapeutic pathway.

Endothelial coagulation inhibitors

As discussed in Sect. 3.8, amine-modified PS-NPs trigger platelet activation via integrin αIIbβ3. This suggests that anti-platelet agents (e.g., integrin inhibitors) or heparin-like substances may prevent thrombogenesis when co-administered with plastically exposed subjects.

Targeted nanocarrier treatment

Innovative nanoparticles conjugated to GP Ibα, mimicking platelet targeting, have demonstrated selective uptake by activated endothelial cells, opening avenues for targeted delivery of antioxidants or anti-inflammatory drugs to diseased vascular sites [152].

Beyond mechanistic insights and potential therapeutic strategies, the implications of MNP-induced cardiovascular toxicity extend to public health and regulatory domains. The detection of MNPs in human cardiovascular tissues underscores the urgent need for standardized monitoring and risk assessment frameworks. From a regulatory perspective, development of exposure guidelines and incorporation of MNPs into environmental health policies will be essential. Clinically, the identification of early biomarkers (e.g., endothelial dysfunction, elevated cardiac enzymes) may support preventive screening and risk stratification in exposed populations. These aspects highlight that the cardiovascular burden of MNPs is not only an experimental concern but also a matter of public health importance.

Conclusions

Micro- and nanoplastics (MNPs) have increasingly emerged as systemic toxicants capable of inducing a broad spectrum of cardiovascular disturbances. As detailed in this review, MNPs can translocate across biological barriers and accumulate in cardiac tissues, where they initiate molecular cascades involving oxidative stress, mitochondrial dysfunction, inflammation, cellular senescence, and apoptosis. These events ultimately contribute to structural and functional cardiac damage, including bradycardia, fibrosis, and vascular injury.

Experimental studies in aquatic and terrestrial animals, as well as human cell models, consistently demonstrate that smaller particles and higher exposure doses correlate with more severe cardiotoxic effects. Recent clinical findings further support the translational relevance of these models, with MNPs now being detected in human atherosclerotic plaques and associated with increased cardiovascular risk. Additionally, the ability of MNPs to adsorb and transport other environmental toxicants raises concern for synergistic toxicity, a factor that may amplify their impact on human health.

Despite these advances, critical gaps remain in understanding the full extent of cardiovascular risks posed by MNPs. There is an urgent need for studies simulating chronic, low-dose exposure at environmentally relevant levels, as well as further investigations into how particle characteristics, aging, and co-exposures influence biological outcomes. Standardized methodologies and sensitive biomarkers for cardiovascular toxicity will be essential to generate comparable data and enable risk assessment.

Considering the global burden of cardiovascular disease, the growing evidence linking MNP exposure to cardiac dysfunction calls for proactive scientific and regulatory responses. Future interdisciplinary research efforts must bridge experimental data with population-level findings, facilitating the development of preventive strategies and therapeutic interventions aimed at mitigating the cardiovascular consequences of MNP exposure.

In addition to experimental evidence, the translational relevance of MNP cardiotoxicity calls for proactive public health measures and regulatory oversight. Standardized exposure monitoring, integration into cardiovascular risk assessments, and early diagnostic strategies are critical steps toward mitigating the potential clinical impact of MNP exposure.

Limitations

This systematic review has several limitations that must be acknowledged:

1. Lack of Human Clinical Data: Despite growing concern about MNP exposure, direct evidence from human clinical studies remains extremely limited. Most available data are derived from in vitro or animal models, which may not fully replicate human physiological responses.

2. Heterogeneity of Study Designs: Included studies varied widely in terms of exposure duration, particle type, concentration, and organism model, which made quantitative synthesis or meta-analysis unfeasible.

3. Non-Standardized Testing Protocols: The absence of standardized protocols for assessing cardiovascular toxicity of MNPs limits the comparability and reproducibility of findings across studies.

4. Focus on Acute Effects: Most studies examined short-term or high-dose exposures, providing limited insight into the chronic, low-dose exposure scenarios that are more relevant to human environmental exposure.

5. Potential Publication Bias: Studies with positive or significant findings may be overrepresented in the literature, while negative or null results may remain unpublished.

6. Limited Scope of Pollutants: This review focused exclusively on microplastics and nanoplastics. However, real-world exposures often involve complex mixtures with co-contaminants, whose combined effects remain underexplored.

7. This review did not apply a formal risk-of-bias tool due to methodological heterogeneity among included studies. Nevertheless, many reports exhibited small sample sizes, incomplete particle characterization, and variable exposure protocols, which may affect reproducibility. Future systematic reviews could benefit from structured appraisal frameworks such as SYRCLE for animal studies.

8. This review was limited to English-language publications, reflecting a predefined inclusion criterion based on the linguistic capacity of the research team. While this ensured consistency and reliability in data extraction, it may have introduced language bias by excluding potentially relevant studies published in other languages. Moreover, no formal publication bias assessment was performed, and therefore studies with null or negative results may be underrepresented.

Future directions

To advance our understanding of MNP-induced cardiovascular toxicity and improve health risk assessment frameworks, we recommend the following:

1. Standardization of Methodologies: Development of internationally accepted protocols for evaluating MNP toxicity—especially for cardiovascular outcomes—is urgently needed.

2. Long-term and Low-dose Exposure Studies: Future research should focus on chronic exposure at environmentally relevant doses to better mimic real-life human exposure conditions.

3. Mechanistic Insights in Human Models: Utilization of human-derived cardiac organoids, induced pluripotent stem cells (iPSCs), and organ-on-a-chip platforms can bridge the gap between animal studies and human relevance.

4. Inhalation and Airborne Exposure Studies: Given the rising concern over airborne MNPs, more in vivo studies focusing on inhalation routes and their cardiovascular effects are warranted.

5. Multi-pollutant Interactions: Investigations should explore the synergistic or antagonistic effects of MNPs with other environmental pollutants such as heavy metals, PAHs, and endocrine disruptors.

6. Biomarker Identification: Identification of early biomarkers (e.g., altered heart rate, blood pressure, cardiac enzymes) associated with MNP-induced cardiovascular stress may support early diagnosis and monitoring strategies.

7. Epidemiological Studies: Large-scale human cohort studies are essential to establish a causal link between MNP exposure and cardiovascular morbidity or mortality.

Abbreviations

MNPs

Micro- and Nanoplastics

MPs

Microplastics

NPs

Nanoplastics

PS-NPs

Polystyrene Nanoparticles

ROS

Reactive Oxygen Species

eNOS

Endothelial Nitric Oxide Synthase

NO

Nitric Oxide

NAC

N-Acetylcysteine

LVOT

Left Ventricular Outflow Tract

NLRP3

NOD-, LRR- and Pyrin Domain-containing Protein 3 (inflammasome)

NF-κB

Nuclear Factor Kappa B

Wnt/β-catenin

Wingless/Integrated Pathway with β-catenin

cGAS-STING

Cyclic GMP-AMP Synthase – Stimulator of Interferon Genes

PAI-1

Plasminogen Activator Inhibitor-1

αIIbβ3

Integrin αIIbβ3 (platelet receptor)

PRISMA

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

Authors’ contributions

F. J: Writing – review & editing, Data curation, Preparation of article figure, N. J: Writing – review & editing. M.K: Writing – review & editing, Investigation. P.R. and Z.M: Writing. Sobhan Nardast: Writing – review & editing. B.A and A.Z: Writing – review & editing.

Funding

N/A.

Data availability

Data are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.