Abstract

Microplastics (MPs; 1 nm to 5 mm) and NPs (Nanoplastics; 1 nm to 1000 nm) have become pervasive environmental pollutants, with continuous human exposure occurring via ingestion, inhalation, and dermal contact to a lesser extent. Although their widespread environmental presence is well established, the cardiovascular system remains affected by them an underrecognized target, despite its direct exposure to circulating particles and vulnerability to oxidative stress and chronic inflammation. This systematic review consolidates existing evidence linking MP/NP exposure to cardiovascular toxicity by examining environmental transport mechanisms, bioaccumulation and biomagnification processes, mechanistic toxicology, controlled animal studies, and emerging human clinical data. In accordance with PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines, 54 peer-reviewed articles published between 2018 and 2025 were systematically analyzed. The reviewed evidence demonstrates that MPs/NPs can cross biological barriers and enter systemic circulation, with studies detecting polymer particles in blood, myocardium, and human atherosclerotic plaques, where concentrations are higher than in plaque-free vascular tissue. Mechanistic investigations consistently show that MP/NP exposure induces ~1.5–3-fold increases in reactive oxygen species (ROS), ~20–40% reductions in mitochondrial adenosine triphosphate (ATP) production, endothelial dysfunction characterized by ~25–40% decreases in nitric oxide bioavailability, and activation of inflammatory and pro-fibrotic signaling pathways. Animal models further demonstrate 22–40% increases in blood pressure, myocardial hypertrophy, fibrosis, and enhanced platelet aggregation following chronic exposure to polystyrene MPs. Importantly, recent human studies reported the presence of MPs within vulnerable atherosclerotic plaques and associate MP burden with a significantly elevated incidence of major adverse cardiovascular events, providing emerging clinical relevance.

Despite the convergence of mechanistic, animal, and preliminary human evidence indicating cardiovascular significance, the literature reviewed indicates that the current methods for exposure assessment and risk characterization are still inadequately defined. In the studies analyzed, NPs (less than 1 µm), which consistently exhibit the highest bioavailability and vascular toxicity, are systematically under detected due to methodological constraints, resulting in a probable underestimation of internal doses by one to two orders of magnitude. The dose–response relationships are predominantly based on short-term or high-dose animal models, which have limited applicability to environmentally relevant chronic exposures in humans. Furthermore, while recent clinical investigations associate microplastic accumulation in atherosclerotic plaques with an increase in major adverse cardiovascular events, there is a lack of population-level longitudinal data. Collectively, these findings highlight the necessity for standardized high-resolution analytical techniques, unified biomonitoring protocols, and regulatory frameworks that explicitly incorporate cardiovascular endpoints into the risk assessment of MNPs.

ABBREVIATIONS

α-SMA — Alpha-smooth muscle actin

Alveolar regions — The tiny air sac areas in the lungs where oxygen and carbon dioxide are exchanged between air and bloodstream.

AMI — Acute myocardial infarction

ATP — Adenosine triphosphate

BPA — Bisphenol A

CAT — Catalase

Cd — Cadmium

CDK5 — Cyclin-dependent kinase 5

CK-MB — Creatine kinase–MB

CVD — Cardiovascular disease

DEHP — Di(2-ethylhexyl) phthalate

ECM — Extracellular matrix

eNOS — Endothelial nitric oxide synthase

Endothelial dysfunction — Impaired functioning of the endothelium (the inner lining of blood vessels), often reducing its ability to regulate blood flow and inflammation.

Epidemiological studies — Research investigations that examine patterns, causes, and health effects of diseases within populations.

Epithelial barriers — Protective layers of epithelial cells that line organs and body surfaces, acting as a barrier against pathogens, toxins, and physical damage.

FTIR — Fourier-transform infrared spectroscopy

GPx — Glutathione peroxidase

Human atherosclerotic plaques — Fatty, cholesterol-rich deposits that build up within human arteries, narrowing and hardening blood vessels.

HQ — Hazard quotient

IL-1β — Interleukin-1 beta

IL-6 — Interleukin-6

LOAEL — Lowest-observed-adverse-effect level

MACE — Major adverse cardiovascular events

MAPK — Mitogen-activated protein kinase

MCP-1 — Monocyte chemoattractant protein-1

MDA — Malondialdehyde

Mechanistic toxicology — The study of how toxic substances cause harmful effects in the body at molecular, cellular, and biochemical levels.

MNP / MNPs — Microplastics and NPs

MP / MPs — Microplastics

Myocardial hypertrophy — Thickening or enlargement of the heart muscle, usually caused by increased workload such as high blood pressure or heart disease.

Myocardium — The muscular middle layer of the heart wall responsible for contracting and pumping blood.

NO — Nitric oxide

NOAEL — No-observed-adverse-effect level

NP / NPs — NPs

NR — Natural rubber

Nrf2 — Nuclear factor erythroid 2–related factor 2

Oxidative stress — Cellular damage caused by an imbalance between reactive oxygen species (free radicals) and the body’s antioxidant defenses.

OECD — Organization for Economic Co-operation and Development

PA — Polyamide

PA-66 — Nylon-66 (polyamide 66)

PAHs — Polycyclic aromatic hydrocarbons

PCBs — Polychlorinated biphenyls

PE — Polyethylene

PET — Polyethylene terephthalate

PFAS — Per- and polyfluoroalkyl substances

PM₂.₅ — Fine particulate matter ≤2.5 µm

POPs — Persistent organic pollutants

PP — Polypropylene

PRISMA — Preferred Reporting Items for Systematic Reviews and Meta-Analyses

PS — Polystyrene

Py-GC/MS — Pyrolysis gas chromatography / mass spectrometry

Pb — Lead

PVC — Polyvinyl chloride

RfD — Reference dose

ROS — Reactive oxygen species

SBR — Styrene-butadiene rubber

SOD — Superoxide dismutase

Terrestrial flux assessments — Measurements and analyses of how substances (such as pollutants, nutrients, or particles) move across land environments and ecosystems.

TGF-β — Transforming growth factor beta

TNF-α — Tumor necrosis factor alpha

VEGF — Vascular endothelial growth factor

WHO — World Health Organization

1. Introduction

Recent cardiovascular-focused reviews report that global plastic production reached ~400.3 million metric tons in 2022, with projections estimating ~13.2 billion tons of plastic waste in ecosystems by 2050, substantially increasing MP/NP exposure potential [20]. Valued for durability, cost, and versatility, these same properties make plastics a persistent pollutant. Plastic waste fragments into smaller particles, notably MPs (1 nm to 5 mm) and NPs (1 nm to 1000 nm). Their presence in water, soil, and air suggests a “plastic age” [49]. This review examines the environmental sources and pathways of MPs, their transfer to humans, evidence for cardiovascular toxicity, and critical research gaps.

Humans are exposed to MNPs through multiple pathways, as they contaminate water, food, and air globally [36, 37, 38, 8, 9]. Environmental source apportionment shows that >80% of MPs originate from land-based sources, while <20% derive from marine activities, highlighting the dominance of urban and industrial emissions [21]. Contamination arises from specific point sources, like wastewater, textile fibers, cosmetic beads, and tire wear [46, 9], and diffuse non-point sources such as agricultural plastics and sludge fertilizers [33]. Some examples of these in daily life are like bottled water, toothpaste, laundry fibers, and much more. Their long-range transport is confirmed by detection in Arctic ice and remote snow [1], making environmental exposure widespread and unavoidable.

Figure 1: Classification of Plastics, MPs, and NPs: Sources, Persistence, and Biological Relevance

Exposure to MNPs occurs through multiple routes due to their widespread environmental distribution. They can permeate soils, crops, and food chains, leading to bioaccumulation. Food processing and packaging also serve as contamination sources, paralleling pathways of other pollutants like heavy metals and persistent organic pollutants (POPs) [2, 23, 24]. Inhalation of atmospheric particles is another significant route [1], while dermal absorption is a plausible pathway in high-concentration occupational settings. Atmospheric exposure assessments indicate that indoor air MPs account for ~4% of airborne particles inhaled, with individuals inhaling up to ~130 microplastic particles per day [19]. Figure 1 illustrates the classification of plastics, MPs, and NPs on the basis of their sources, persistence, and biological relevance.

MNPs accumulate and magnify through the food chain. Ingested by organisms like plankton, they transfer through fish and marine mammals, ultimately reaching humans [2, 23, 24]. Comprehensive exposure modeling estimates that adults ingest ~39,000–52,000 microplastic particles annually via food and water, rising to ~74,000–121,000 particles per year when inhalation is included [52]. Their resilience, hydrophobicity, and ability to absorb other contaminants increase their pervasiveness in biological tissues [8]. Unlike biodegradable materials, MPs persist, raising concerns about bioaccumulation, prolonged exposure, and biomagnification.

MPs contain toxic additives like bisphenol A and phthalates, which can disrupt endocrine function. Controlled animal studies demonstrate that polystyrene microplastic exposure increased mean blood pressure by 22–40% and induced myocardial hypertrophy after 42 days, directly linking MP exposure to cardiovascular dysfunction [15]. They also act as carriers for other contaminants, including heavy metals, PAHs, and pathogens, heightening their toxicity [45]. This dual role exacerbates biological impacts. Recent reviews highlight key toxic mechanisms, such as oxidative stress, mitochondrial dysfunction, and immune modulation [36, 37, 38, 8]. Table 1 summarizes major sources of MPs, their presence in environmental media, and associated routes of human exposure and health implications.

Table 1: Sources, Environmental Media, and Human Exposure to MPs

The growing evidence of MNPs harming human health has intensified research into organ-specific impacts, particularly on the cardiovascular system, a key, complex body system comprised of the heart, blood vessels (arteries, veins, and capillaries), and blood. These particles have been detected in human tissues, including the bloodstream and placenta, while animal studies show that chronic exposure can cause vascular inflammation, disrupt lipid metabolism, and accelerate atherosclerosis [26, 27, 54]. The cardiovascular system is vulnerable due to direct contact with circulating particles and its reliance on endothelial and inflammatory balance. Given that cardiovascular disease is the leading global cause of death, as stated by WHO, the potential link to microplastic exposure warrants urgent investigation.

Substantial research gaps remain. Global MP distribution is mapped, but measurement of human exposure is inconsistent and methodologically limited [9]. Critical uncertainties exist regarding particle size distribution, safe exposure limits, and chronic health effects [36, 37, 38]. Few studies incorporate multiple exposure routes (ingestion, inhalation, dermal) into holistic risk assessments. The mechanisms of bioaccumulation and biomagnification are unclear, complicated by varied particle characteristics. Despite widespread detection, reviews emphasize that no standardized analytical framework exists for NPs, and current estimates likely underestimate exposure by 10–100× due to detection limits below 1 µm [45]. A notable lack of epidemiological studies directly links MP/NP exposure to cardiovascular or other chronic diseases [26, 27, 54]. Bridging these gaps requires interdisciplinary strategies integrating environmental monitoring, toxicology, and population-based research. Figure 2 shows the main pathways of human exposure to MPs and their effects on cellular processes and cardiovascular health.

Figure 2: MPs Exposure Pathways, Target Organs, and Health Impacts

With rising plastic production, the detrimental impacts of MNPs on the environment and human health are increasingly evident as stated in OECD. Given that cardiovascular disease accounts for ~32% of global mortality, even modest MP-associated cardiovascular risk could translate into substantial population-level health impacts [36]. A comprehensive strategy integrating monitoring, toxicology, clinical oversight, and regulation is essential [2]. This review, 1, elaborates on the sources and environmental pervasiveness of MNPs, 2, explains their entry and movement through the food chain via bioaccumulation and, 3, critically evaluates the evidence linking exposure to human health and particularly cardiovascular disease, while highlighting key knowledge gaps. By bridging environmental and biomedical research, this work aims to, 5, establish a framework to confront this critical pollution challenge.

2. Methodology

This systematic review evaluates the cardiovascular effects of microplastics and nanoplastics using the PRISMA framework to ensure transparency, replicability, and methodological rigor throughout the study selection and analysis process, with each stage from initial database identification to final inclusion, carefully documented to minimize bias and strengthen reliability. The analysis synthesizes findings from 54 peer-reviewed articles published between 2018 and 2025, representing the most current research on the prevalence, exposure pathways, and health implications of MNPs for the human cardiovascular system, while integrating both mechanistic and epidemiological perspectives to provide a comprehensive understanding of their biological impact. The search strategy was designed to be both broad and targeted, employing multiple academic databases and strategically combining keywords such as MPs, NPs, cardiovascular toxicity, oxidative stress, atherosclerosis, and human exposure using Boolean operators to capture studies addressing both direct and indirect cardiovascular effects. Inclusion criteria focused on studies investigating cardiovascular outcomes or related mechanisms, including inflammation, endothelial dysfunction, and lipid metabolism disruption, while exclusion criteria removed studies lacking biological relevance or sufficient methodological detail; data extraction emphasized variables such as particle size, concentration, exposure route (ingestion, inhalation, or dermal), and observed cardiovascular effects. By synthesizing this body of evidence through a structured and systematic approach, the review not only consolidates current knowledge but also highlights critical gaps—particularly the scarcity of long-term human studies and standardized exposure assessment methods—thereby establishing a strong foundation for understanding MNPs as emerging contributors to cardiovascular disease and guiding future research directions.

3. Environmental Sources, Transport, Exposure Pathways, and Systemic Fate of Microplastics

Microplastics originate from both primary and secondary sources. Primary MPs are intentionally manufactured microscopic particles used in industrial applications, cosmetics, and pharmaceuticals, whereas secondary MPs form through the environmental fragmentation of larger plastic debris via ultraviolet radiation, mechanical abrasion, and thermal degradation. Environmental inventories indicate that secondary MPs constitute the majority of environmental plastic particles, reflecting the continuous degradation of consumer plastics.

Industrial and urban activities represent major contributors to MP emissions. Common sources include textile fiber shedding during laundering, tire wear particles, wastewater discharge, and microbeads from personal care products. Because many polymers persist for decades, environmental reservoirs of plastic particles continue to accumulate, creating sustained exposure risks.

Once released, MPs are transported across aquatic, terrestrial, and atmospheric compartments. Rivers and wastewater systems deliver plastics to marine environments, where buoyant polymers such as polyethylene and polypropylene remain near the surface, while denser polymers settle in sediments. Terrestrial environments receive MPs through agricultural plastic use, sewage sludge application, irrigation with contaminated water, and atmospheric deposition, making soils major environmental reservoirs. Atmospheric transport also contributes significantly to global distribution, allowing MPs to travel long distances before deposition.

Environmental weathering alters particle properties and increases their biological relevance. Fragmentation processes generate progressively smaller particles, including nanoplastics, which exhibit greater mobility, bioavailability, and potential for biological interaction. Aging processes such as ultraviolet oxidation modify particle surfaces and increase their capacity to adsorb environmental contaminants including heavy metals, persistent organic pollutants, and plastic additives.

3.1 Oxidative Stress as a Central Initiator of Cardiovascular Injury

Human exposure to MPs and NPs occurs primarily through ingestion and inhalation, with dermal contact representing a comparatively minor pathway.

Ingestion is widely considered the dominant exposure route. MPs enter the human body through contaminated food, drinking water, and food packaging materials. Marine organisms, particularly filter feeders such as shellfish, accumulate MPs and transfer them through trophic food chains. Exposure modeling estimates that humans ingest approximately 39,000–52,000 microplastic particles annually, increasing to 74,000–121,000 particles per year when inhalation exposure is included.

Inhalation represents another important exposure pathway, particularly in indoor environments where synthetic fibers from textiles, carpets, and household materials accumulate in dust and air. Airborne MPs may deposit throughout the respiratory tract depending on particle size and shape. Larger particles are typically cleared through mucociliary transport, whereas smaller particles may penetrate deeper into lung tissue. Studies estimate that individuals may inhale up to ~130 microplastic particles per day, primarily originating from synthetic fibers and urban particulate sources such as tire wear.

Dermal exposure generally contributes less to total MP exposure but may occur through personal care products, contaminated water, and occupational settings involving plastic processing or textile production. While intact skin provides an effective barrier to most MPs, smaller nanoplastic particles may penetrate through damaged skin or hair follicles under prolonged exposure conditions.

Collectively, these exposure pathways indicate that human contact with MPs and NPs is continuous and multi-route, supporting growing evidence of systemic distribution of plastic particles within biological tissues.

4. Mechanistic Basis of Cardiovascular Toxicity

4.1 Oxidative Stress as a Central Initiator of Cardiovascular Injury

Oxidative stress is a primary response to MP and NP exposure. These particles generate excessive reactive oxygen species (ROS), overwhelming antioxidant defenses and leading to lipid peroxidation, protein denaturation, and DNA damage in vascular and cardiac cells [20, 51]. Experimental models demonstrate that MP exposure increases intracellular ROS levels by ~1.5–3.0-fold in vascular and cardiac cells relative to controls, exceeding endogenous antioxidant buffering capacity [20].

Chronic oxidative stress disrupts lipid balance and increases vascular inflammation, key to atherosclerotic plaque formation. Preclinical studies show that polystyrene MPs cause ROS buildup in cardiomyocytes and endothelial cells, triggering apoptosis and impairing mitochondrial function [20]. This underscores their role as environmental drivers of cardiovascular oxidative damage, particularly under realistic, chronic low-dose exposure. In cardiomyocyte models, chronic polystyrene MP exposure results in significant mitochondrial membrane potential loss (>30%) and increased apoptotic indices, confirming sustained oxidative injury [20].

4.2 Mitochondrial Dysfunction and Cardiomyocyte Injury

Following ROS accumulation, mitochondria become key targets for MP and NP toxicity. Particles disrupt mitochondrial membrane potential, impair ATP production, and cause morphological damage, including swelling, cristae disorganization, and membrane rupture [20]. Animal studies show that MP exposure reduces myocardial ATP production by ~20–40%, accompanied by mitochondrial swelling and cristae disruption [20].

Polystyrene MPs elevate serum cardiac troponin I and CK-MB, biomarkers of myocardial injury, indicating direct damage to myocytes [20]. This mitochondrial dysfunction activates pro-apoptotic proteins (e.g., Bax) and inhibits anti-apoptotic regulators (e.g., Bcl-2), pushing cardiac cells toward irreversible injury and death [26, 27].

These findings align with human cardiovascular pathology, where mitochondrial dysfunction is central to heart failure, ischemic injury, and cardiomyopathy, raising concern that chronic MP exposure may accelerate these processes. Mitochondrial dysfunction contributes to >90% of ATP depletion observed in failing myocardium, indicating that MP-induced mitochondrial damage targets a core pathway in human heart disease [36].

4.3 Inflammatory Activation and Endothelial Dysfunction

Oxidative stress and mitochondrial damage trigger endothelial activation. MP and NP exposure increases inflammatory cytokines like IL-6, TNF-𝛼, and MCP-1, promoting leukocyte adhesion, endothelial permeability, and vascular inflammation [20].

A dysfunctional endothelium has reduced nitric oxide (NO) bioavailability due to disrupted eNOS signaling. This exacerbates vascular imbalance, promoting hypertension, increased stiffness, and impaired flow-mediated responses.

Due to their small size, NPs can infiltrate endothelial junctions, accumulate in vascular tissue, and trigger endothelial apoptosis and microvascular remodeling. This fosters a pro-atherogenic environment that interacts synergistically with traditional risk factors.

4.4 Myocardial Fibrosis, Wnt/β-Catenin Activation, and Structural Remodeling

Chronic MP and NP exposure leads to structural cardiac remodeling. MPs stimulate fibroblasts, promoting excessive extracellular matrix production, especially collage, leading to myocardial fibrosis [20, 50].

This fibrosis is partly driven by activation of the Wnt/𝛽-catenin signaling pathway, which regulates fibroblast proliferation and profibrotic gene expression [54]. Chronic fibrosis reduces myocardial compliance, disrupts electrical conduction, and increases the risk of heart failure and arrhythmia.

Figure 3: Mechanistic Diagram of Cardiovascular Toxicity

4.5 Microvascular Toxicity, Vascular Aging, and Hematologic Impairment

MNPs also affect microvascular function. They induce hemolysis by damaging red blood cell membranes, increasing oxidative susceptibility, and altering erythrocyte deformability [54].

MP-induced endothelial damage also disrupts the balance between angiogenic and anti-angiogenic factors like VEGF, promoting abnormal vascular proliferation or regression.

ROS-activated cyclin-dependent kinase 5 (CDK5) accelerates premature vascular aging, directly linking microplastic exposure to endothelial senescence [20].

MP accumulation in the gut also alters the microbiome, promoting dysbiosis linked to increased cardiovascular risk, including hypertension and atherosclerosis [20]. Figure 3 illustrates the molecular and cellular mechanisms by which MNPs may contribute to cardiovascular toxicity and disease.

4.6 Thrombus Formation, Platelet Activation, and Pro-Coagulant Effects

MPs promote thrombogenesis by activating platelets, binding to surface receptors, and enhancing adhesion, degranulation, and aggregation which are key steps in thrombus formation [20].

In vivo studies show ultrafine particles rapidly induce platelet aggregation and accelerate clot propagation. MPs also disrupt endothelial antithrombotic functions, shift hemostatic balance toward coagulation, and impair fibrinolysis [27, 28]. Together, these factors increase the likelihood of:

• coronary thrombosis
• ischemic stroke
• microvascular occlusion
• postoperative thrombotic complications

This mechanism supports emerging clinical evidence linking MP exposure to higher major adverse cardiovascular event (MACE) incidence.

4.7 Tissue Accumulation, Atherosclerotic Plaques, and Clinical Evidence of Cardiovascular Risk

Recent human studies confirm MPs accumulate in cardiovascular tissues. Using Py-GC/MS, researchers have identified PET, PA-66, and PVC in human arteries, with higher concentrations in atherosclerotic plaques than in plaque-free tissue [27, 28].

Further studies using infrared chemical imaging and electron microscopy have identified MPs in cardiac tissue from surgical patients. Some polymers reflect environmental exposure, while others may originate from surgical instruments [20].

These findings confirm mechanistic pathways, showing MPs circulate and infiltrate human vascular and myocardial tissues. Their presence within atherosclerotic plaques suggests a direct role in plaque progression, instability, and thrombosis, supporting the link between MP burden and increased risk of myocardial infarction and stroke. Table 2 summarizes proposed mechanistic pathways linking microplastic exposure to cardiovascular toxicity across experimental and human evidence.

Table 2: Mechanistic Pathways of MPs-Induced Cardiovascular Toxicity

5. Evidence from Animal and Human Studies
5.1 Animal Models

Animal models have been essential for defining MP/NP cardiovascular toxicity. Rodent models are most common, while transparent zebrafish allow real-time tracking. Exposure routes include oral gavage, contaminated water, and inhalation, using particles like PS, PE, PP, PET, and tire wear across sizes from 50 nm to 50 μm [50, 53]. Figure 4 illustrates the progression from microplastic accumulation in cardiac tissue to cellular injury and fibrotic remodeling.

Figure 4: Histological and Functional Representation of MP-Induced Cardiac Damage