From Environment to Endothelium: The Role of Microplastics in Vascular Aging

Abstract

Microplastics, synthetic polymer particles measuring less than 5 mm, have become a widespread environmental pollutant, raising concerns over their possible effects on human health. Growing evidence links MPs to vascular aging and cardiovascular disease beyond their ecological toxicity. Upon inhalation, ingestion, or skin contact, microplastics can traverse biological barriers, circulate systemically, and accumulate in vascular tissues. Experimental investigations indicate that MPs, especially polystyrene and polyethylene in nano- and micro-sized forms, induce oxidative stress, mitochondrial dysfunction, and chronic inflammation. These disruptions activate redox-sensitive signaling pathways, such as NF-κB and NLRP3 inflammasome, causing endothelial dysfunction, vascular smooth muscle modulation, and foam cell production, indicating early vascular aging. Animal models and in vitro studies have consistently shown endothelial activation, increased cytokine production, and changes in vascular tone after exposure to MPs. Initial human research has detected microplastics in blood, thrombi, and atherosclerotic plaques, which correlate with negative cardiovascular outcomes and systemic inflammation. Notably, recent research suggests that the gut microbiota and antioxidant systems may play a role in adaptive reactions, although these processes are still not fully understood. MP-induced vascular toxicity is covered in this interdisciplinary review, highlighting molecular pathways, experimental data, and translational gaps.

1. Introduction

Global plastic production has consistently increased, reaching 369 million tons in 2020, which is a notable growth from prior years [1]. Plastics are preferred for their adaptability, and are utilized in applications ranging from medical instruments to food packaging. Their affordability and simplicity of manufacture render them essential in several industries [2]. The contemporary lifestyle, marked by a need for convenience, has resulted in a heightened dependence on single-use plastics, including cups, cutlery, and packaging [3]. The resilience of plastics, although advantageous for application, presents significant challenges for waste disposal. A significant amount of plastic garbage is deposited in landfills, exacerbating pollution [4]. The degradation of these polymers is an increasing issue, since they are ubiquitous in all environmental compartments and provide threats to ecosystems and human health [5,6].

In 2004, Richard Thompson and his team at the University of Plymouth used the term ‘microplastic’ to refer to tiny plastic particles present in marine sediments. This drew attention in scientific and policy-making circles, resulting in extensive utilization and investigation of the subject [7]. Microplastics (MPs) are described as plastic particles measuring less than 5 mm, either from the degradation of bigger plastic materials or produced intentionally as microscopic particles for commercial purposes [8,9]. They are present in multiple forms, such as fibers, fragments, and beads, and can be located in a range of environments, including oceans and soils [10,11,12]. MPs are a complex mixture containing a range of production additives, such as plasticizers, biocides, flame retardants, stabilizers, antioxidants, and organic pigments. Numerous additives are loosely attached to the polymer matrix and may leak into the surrounding areas. Moreover, the extensive surface area and hydrophobic characteristics of MPs enhance their function as mobile platforms for the release of intrinsic additives and the adsorption and transport of external pollutants [13,14]. Their physicochemical features enable the adsorption and co-transport of heavy metals, persistent organic pollutants, and genetic material such as antibiotic resistance genes, hence augmenting their hazardous potential [15,16]. In a study conducted recently, the effect of microplastics and nanoplastics on the soil microbial balance and plant health in agricultural and natural lands has been determined [17]. Microplastics have the potential to harm the ocular tissues and impose health risks that are beyond cardiovascular disease. Their bioaccumulation can lead to oxidative stress and cause inflammatory ocular diseases [18]. They can be found in the air, food, and water, and inhaled as well as ingested by people [19,20]. Dermal contact represents a potential route of exposure, albeit less significant, especially in environments characterized by high levels of plastic pollution [20].

Vascular aging represents a significant biological process marked by structural and functional changes in the vasculature, which play a crucial role in the development of cardiovascular disease, the leading cause of morbidity and mortality worldwide [21]. The aging process is characterized by arterial stiffness, endothelial dysfunction, and reduced angiogenic potential [22]. The mechanisms through which MPs contribute to vascular aging are complex and play a crucial role in the pathogenesis of cardiovascular diseases. A recent study indicates that MPs may induce oxidative stress and inflammation, which are significant contributors to cardiovascular diseases. Mitochondrial dysfunction and apoptosis resulting from these processes contribute to cardiovascular damage [23]. Research indicates the presence of MPs in atherosclerotic plaques, which is associated with a heightened risk of major adverse cardiovascular events (MACE) [24].

Although MPs are widely acknowledged as environmental pollutants, their particular influence on vascular aging has not been thoroughly investigated. The existing literature predominantly emphasizes the acute toxicological effects of MPs, frequently neglecting their possible chronic implications for vascular health. This review aims to address significant gaps by synthesizing current research on the interaction between MPs and vascular aging processes. We seek to clarify the processes by which MPs induce oxidative stress, inflammation, and endothelial dysfunction, which are critical in the advancement of vascular aging. Furthermore, we will investigate possible adaptive responses to low-level microplastic exposure, and contrast these results with the largely negative perspectives. By comprehensively reviewing both experimental and epidemiological data, this review will provide novel insights into the vascular implications of microplastic exposure and suggest actionable public health strategies to mitigate these risks. Our ultimate goal is to balance the understanding of risks with an evaluation of possible adaptive responses, offering a dual perspective on the health implications of microplastics. This approach not only enhances our understanding of environmental contaminants but also underscores the necessity for integrated research and policy interventions that address both public health and environmental sustainability.

Literature Search

A systematic search of the literature was conducted to find peer-reviewed research on microplastics’ and nanoplastics’ effects on vascular aging and cardiovascular health. The search used PubMed, Scopus, Web of Science, and Google Scholar to find articles from January 2000 to April 2025. Search terms included combinations of keywords including “microplastics,” “nanoplastics,” “vascular aging,” “endothelial dysfunction,” “oxidative stress,” “inflammation,” “cellular senescence,” “atherosclerosis,” “arterial stiffness,” and “cardiovascular risk,” together with terms such as “in vitro,” “animal model,” and “human study,” utilizing Boolean operators AND and OR for search effectiveness. English-language studies on microplastic exposure and vascular or cardiovascular outcomes with mechanistic insights such as redox-sensitive signaling pathway activation or cellular dysfunction, met the criteria. Our research included in vitro, in vivo, and human investigations.

2. Source and Exposure

The two main categories of MP sources are primary and secondary microplastics. Primary microplastics are deliberately produced small particles, including microbeads utilized in cosmetics and personal care items, along with microfibers released from synthetic textiles during laundering [25]. Fibrous microplastics, a category of primary microplastics, are primarily derived from synthetic textiles. Fibers are released into the environment via the washing and wearing of clothing, thereby contributing to microplastic pollution in terrestrial and aquatic ecosystems [26]. Secondary microplastics primarily result from the degradation of larger plastic items, including bottles, bags, and various consumer goods. This decomposition results from physical, chemical, and biological processes in the environment [27]. Urban environments play a substantial role in secondary microplastic pollution, primarily through litter such as cigarette butts and plastic packaging. These materials deteriorate over time, resulting in the release of microplastics into the environment [28].

Microplastics can be transported via the atmosphere, ultimately settling in diverse environments, including remote terrestrial and aquatic ecosystems. This pathway illustrates the interrelation of various environmental compartments [26]. Wastewater treatment plants serve as important pathways for microplastics from both household and industrial sources. Although certain microplastics are eliminated during treatment processes, a significant quantity is discharged into aquatic environments or accumulates in sewage sludge and is frequently utilized as agricultural fertilizer [29].

2.1. Exposure of Microplastics into the Human Body

Human exposure to MPs occurs through multiple principal channels, including ingestion, inhalation, and skin contact. MPs are frequently present in many food items, such as seafood, bottled water, and processed meals. These particles infiltrate the food chain through environmental pollution and are eaten by people upon ingesting these items [19,30]. A major source of microplastic consumption is drinking water, with research indicating contamination in both bottled and tap water. The broad prevalence of MPs in water sources is mostly attributable to plastic packaging and waste management challenges [31]. Sea salt and other condiments have been recognized as vectors for microplastics, hence increasing dietary exposure. This results from the pollution of marine ecosystems from which these items are derived [30]. Upon being introduced to the body, MPs rapidly adsorb biomolecules within seconds, forming a protein corona comprising plasma proteins and extracellular organic compounds. It is a corona that stabilizes MPs and influences their biological identity, uptake, circulation, and interaction with cells. While extracellular polymeric substances and natural organic matter enhance the stability of microplastics in the environment, they do not exhibit the same effect within the human body, as aggregation by divalent ions, prevalent in environmental matrices, typically does not occur under physiological ionic conditions in humans, resulting in microplastics remaining dispersed in bodily fluids [15,18].

Microplastics are also prevalent in the atmosphere, especially in urban and industrial regions, where they may be breathed. Indoor surroundings add to exposure by releasing microplastics from synthetic fabrics and household dust [20,31]. Inhaled MPs may accumulate in lung tissues, potentially resulting in respiratory complications and inflammatory reactions. This mechanism is important because microplastics can penetrate respiratory barriers [32]. The binding of MPs to target cells involves a selective process called cellular uptake, which typically occurs through endocytic pathways, including, but not limited to, clathrin-mediated endocytosis, macropinocytosis, and phagocytosis. The uptake pathway, influenced by particle size, surface charge, and protein corona composition, will determine the effectiveness and nature of cellular recognition and uptake [18]. Microplastics are used in several personal care products, including exfoliants and lotions, resulting in skin exposure [33]. Direct exposure to polluted water and air may lead to skin contact; however, the magnitude and effects of this route are less comprehensively studied compared to ingestion and inhalation [33] [Figure 1].

2.2. Microplastic Exposure and Detection in Humans

The higher density of MPs found on land leads to greater exposure risks in highly populated areas. The accumulation of microplastics in remote locations such as Antarctica and the Arctic remains lower than in other regions [34]. Asian rivers show higher levels of microplastics in their surface waters compared to Euro-American rivers, whereas Euro-American rivers have more microplastics in their sediments. The difference in microplastic distribution relates directly to the ongoing urban development, together with waste management methods [35]. Standardized beach sampling methods show that concentrations of microplastics demonstrate substantial regional differences since their levels depend on plastic pollution origins, including river sources and ocean currents [36]. Residents of urban areas face higher microplastic exposure levels because their environment becomes polluted through traffic emissions, as well as industrial operations and domestic activities [34]. Surface water pollution with microplastics is higher in lower-middle and upper-middle-income nations, while sediment contamination reaches greater levels in high-income countries due to differences in environmental management policies [35]. Neonates, together with infants, demonstrate high sensitivity to microplastic exposures through indoor ingestion and inhalation [37]. Despite adults gathering more microplastics throughout their lives due to extended exposure, children face a substantial danger of exposure to microplastics [38]. Various settings where people consume or inhale affect the quantity of microplastics they encounter, which indicates how common this issue truly is throughout different age groups.

Detecting MPs in human tissues is crucial for assessing exposure levels and associated health consequences. Spectroscopic techniques serve as the principal means for detection. Raman spectroscopy employs distinctive molecular signatures to detect plastics without modifying the sample, although the technique requires thorough sample preparation, and background signals must be considered [39]. Fourier-transform infrared spectroscopy (FTIR) is the second most used technique for detecting particles of size ~10 μm and various types of plastic, although its efficacy diminishes when the particles are covered by tissue material. Laboratories integrate Raman spectroscopy with FTIR spectrometry as both methods complement one another, with Raman identifying dark and non-polar polymers and FTIR distinguishing particular chemical groups. Researchers employ the combination of Py-GC/MS for analyzing tiny plastics or whole plastic samples [40]. Instruments like laser direct infrared (LDIR) imaging and electron microscope spectroscopy have improved the precision and efficiency of plastic detection [41]. The standard procedure in most investigations includes tissue digestion, subsequent filtering, particle inspection, and spectroscopic analysis, resulting in final verification using Py-GC/MS for plastic quantification.

3. Negative Impacts on Vascular Health

Microplastics, due to their microscopic size and capacity for bypassing biological barriers, can infiltrate the human body and accumulate in diverse tissues, including vascular tissues [42]. The buildup of microplastics in vascular tissues is accelerated by their capacity to interact with biological processes. They can adhere to plasma proteins, facilitating their delivery to distant organs, including the cardiovascular system [43]. This connection not only promotes their accumulation but also initiates a cascade of cellular reactions that lead to oxidative damage and inflammation.

3.1. Oxidative Stress and Inflammation

By activating immune cells such as macrophages, these particles trigger the generation of ROS, which becomes part of the inflammatory process. Increased inflammation leads to the development of pro-inflammatory cytokines that strengthen oxidative stress conditions [44]. The activity of mitochondria is compromised by MPs, which leads to increased ROS production. The neutralizing capacity of antioxidant enzymes SOD and GPx decreases usually as ROS develops [45]. An excess of ROS generates damage to cellular DNA, proteins, and lipids, which leads to both cell dysfunction and mortality.

Microplastic-induced oxidative stress processes in vascular tissues have been successfully studied by researchers using in vitro laboratory methods. The research by Simmons et al. demonstrated that human umbilical vein endothelial cells (HUVECs) encounter polystyrene nanoplastics, which causes ROS overproduction and breaks down mitochondrial functions while triggering cell death [46]. Research using vascular smooth muscle cells (VSMCs) has proven that microplastics create ROS production, destroy cellular mitochondria, and initiate inflammatory responses [47]. In vitro studies have been supported by systematic findings produced through animal model research for microplastic exposure. The research using mice to explore exposure to polystyrene microplastics showed that it raises oxidative stress markers MDA and 4-HNE while altering lipid metabolism and insulin resistance in vascular tissues, which makes individuals more likely to develop cardiovascular diseases [48]. The exposure of zebrafish to polystyrene microplastics leads to cardiovascular toxicity that manifests as pericardial edema, together with increased sinus venosus–bulbus arteriosus distances and tissue damage because of elevated ROS production and apoptosis within cardiovascular tissues [49].

Microplastics cause inflammatory reactions that frequently occur when bloodstream tissues encounter these exposures. The inflammatory response becomes activated through microplastic-caused release of crucial pro-inflammatory mediators interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) [43]. Cytokines activate endothelial cells and direct leukocytes toward the vascular wall for recruitment, among which macrophages and neutrophils participate. The immune cells take microplastics inside their bodies to produce further inflammation-inducing mediators. The inflammatory response is activated strongly in monocytic cells when they encounter microplastics because these exposures increase cytokine quantities and release events [50]. Neutrophils function as the main microplastic-clearing cells, even though their scavenging activities create further inflammation in the body.

The investigation of microplastic-induced vascular inflammation progressed because of in vitro experiments, together with animal models, which identified essential mechanisms in this process. The exposure of mice to polystyrene microplastics results in high cytokine and adhesion molecule expression in their aortas, thus promoting stronger leukocyte adhesion when under flow conditions [50]. The exposure of rats to microplastics leads to vascular damage as indicated by elevated myocardial enzyme levels, followed by measurements of oxidative stress [51]. The cellular reactions to microplastics have been fully investigated through in vitro laboratory analysis techniques. Aortic HCASMCs exposed to aged microplastics experience major oxidative stress along with extensive inflammation that leads to elevated IL-6 and TNF-α protein levels as fundamental inflammatory mediators [52].

3.2. Acceleration of Vascular Aging

The active relationship between oxidative stress and inflammation produces endothelial dysfunction, which forms the basis for vascular aging. Vascular homeostasis maintenance ability decreases in endothelial cells, which leads to worsened vascular decline. The process of aging affects vascular cells through the deterioration of their fundamental functions, where endothelial cells and smooth muscle cells represent the major types [53]. Microplastics increase cellular aging through the mechanism of oxidative stress and inflammation, which results in cellular senescence. The increase in ROS by MPs causes damage to mitochondrial DNA while also affecting mitochondrial functionality. The breakdown produces reduced energy output and elevated oxidative damage that demonstrates traits of aged blood vessels [54]. The aging of blood vessels becomes worse due to sustained inflammation because it causes chemokines and pro-inflammatory cytokines to be released, which activate cellular senescence and apoptosis pathways [55]. Various processes break down vascular functions until early vascular aging becomes established, which substantially increases cardiovascular disease risk.

3.3. Type- and Size-Specific Microplastics and Vascular Aging

Scientific studies show that vascular health suffers the most damage from microplastics having polystyrene and polyethylene structures and particular size dimensions. Polystyrene Microplastic Particles (PSMPs) represent the most frequently detected microplastic type that exists throughout the environment. The research shows that PSMPs activate endothelial cells to produce more adhesion molecules while raising levels of inflammatory cytokines, thereby playing a critical role in vascular aging and inflammation [50]. The PSMPs contribute to vascular calcification, which serves as a sign of vascular aging according to studies performed on humans and animals [56]. Microplastics of high- and low-density polyethylene induce pro-inflammatory responses in vascular smooth muscle cells while causing changes to cellular phenotypes and metabolic characteristics that enhance pro-inflammation [52] status, which contributes to vascular tissue aging.

Microplastic toxicity strongly depends on their physical size. Standards for microplastic toxicity measure the dimensions of these particles because they can enter human tissue cells deeply when they are nanometer-sized. Research shows that small-sized microplastic particles create higher opportunities to cause both inflammatory reactions and oxidative stress conditions that drive vascular aging processes [57]. Smaller particles enhance both oxidative stress and inflammation levels through their path, during which time they induce mitochondrial failure and trigger cell death, which in turn accelerates vascular cell aging. The pathways involving CDK5 signaling enable microplastics to elevate ROS levels, thus contributing to early blood vessel aging [58]. The damage that microplastics inflict on endothelial cells increases vascular permeability and leads to new inflammatory responses that precede various cardiovascular diseases and act as a main aging factor in blood vessels [59]. Microplastic features determine both its acceleration of vascular aging through specific size and type-related mechanisms. Figure 2 shows the summary of pathways related to the effect of MPs on vascular health.

3.4. Experimental and Human Evidence of Microplastic-Induced Vascular Effects

Reports now emphasize the vascular effects of MPs and NPs through research studies using different animal and cell models to investigate their cardiovascular implications. Zhang et al. studied polystyrene nanoplastic exposure in mice, which resulted in considerable vascular toxicity outcomes. The study found that both lipid metabolism changes and arterial wall thickening occurred because PIWI-interacting RNA expression profiles affected cell growth and motility-related signaling pathways [60]. Research showed that co-exposure of mice to MPs together with lead exposure accelerated the progression of aortic medial degeneration through elastic fiber damage and vascular smooth muscle cell depletion [47].

Research on zebrafish embryos exposed to polystyrene microplastics and nanoplastics revealed significant cardiovascular impairment, resulting in decreased heart rate and fluid accumulation in the pericardial sac. Research indicated thrombosis accompanied by significant vascular damage, highlighting the developmental and environmental risks of MP and NP pollution for fetal cardiovascular health [49]. Researchers have investigated the effects of microplastics on cardiovascular health by studying ApoE-/- mice, as this model facilitates the examination of atherosclerosis and cardiovascular disorders due to the animals’ inherent predisposition to hyperlipidemia and atherosclerotic lesions. Research evidence indicates that exposure to PS-NPs accelerates atherosclerotic plaque formation in these animals by enhancing inflammation and oxidative stress processes [61,62]. C57BL/6J mice, a widely utilized model, have played a crucial role in examining PS-MPs’ effects on body weight, fat mass, and insulin resistance, thereby underscoring the varied influences of microplastics on cardiovascular risk factors [63].

Studies examining microplastic-induced vascular processes have predominantly utilized vascular smooth muscle cells along with human umbilical vein endothelial cells. Research indicates that inflammatory pathways are triggered by MPs, which simultaneously exacerbate oxidative stress levels in VSMCs, resulting in worsened cardiovascular disease [52]. PS-NPs disrupt HUVEC functionality by inducing increased ROS levels and diminishing NO availability, hence contributing to endothelial dysfunction [59]. The distribution of kinesin family member 15 (KIF15) functions as a regulatory mechanism for vascular smooth muscle cell migration and apoptosis, which is enhanced by PS-NPs and, therefore, demonstrating the biological pathways that connect microplastics to vascular cell dynamics [61]. The gap in studies between animal models and human biology required the development of cardiac organoids of human origin grown from pluripotent stem cells. According to studies, exposure to microplastics led to the development of enhanced oxidative stress, indicators of inflammation and apoptosis, and collagen accumulation in human cardiac organoids [64]. The combination of data across several biological systems clearly illustrates the intricate effects of microplastics on vascular health.

Table 1. Summary of Experimental Models for Vascular Effects of Microplastics.

Author(s)	Model	Microplastic Type, Size, Dose	Exposure Duration	Vascular End Points	Key Findings
Animal models (in vivo)
Wang X, Jia Z, Zhou X et al. [65]	Mouse (C57BL/6)	Polystyrene (PS) nanoplastics, ~50 nm; surface variants; 0.05–20 mg/kg (oral)	14 days (short-term)	Endothelial integrity, inflammation markers, and coagulation parameters	Exposure caused structural damage to the vascular endothelium and an inflammatory response in mice. Notably, pro-thrombotic effects were observed—nanoplastics induced a prothrombotic state with coagulation dysfunction via activation of the JAK1/STAT3/Tissue Factor pathway.
Wang B, Liang B, Huang Y et al. [66]	Mouse (ApoE−/−)	PS nanoplastics, ~50 nm; 2.5, 25, 250 mg/kg (oral gavage) + high-fat diet	19 weeks (chronic)	Arterial stiffness, atherosclerotic plaque burden, macrophage activation, serum lipid metabolism	Chronic low-dose PS nanoparticle ingestion significantly increased arterial stiffness and promoted atherosclerotic plaque formation in ApoE−/− mice. Treated mice showed enhanced M1 macrophage uptake in lesions and disrupted lipid metabolism, suggesting microplastics exacerbate plaque development via metabolic and inflammatory mechanisms.
Zhou Y, Wu Q, Li Y et al. [64]	Mouse (C57BL/6)	PS microplastics; low human-equivalent dose.	4 weeks (chronic)	Cardiac hypertrophy index, cardiac function	Even at low, human-relevant doses, chronic PS microplastic ingestion induced myocardial hypertrophy and reduced cardiac output in mice. Notably, the same study also showed similar cardiotoxic effects in human cardiac organoids.
Li Z, Zhu S, Liu Q et al. [67]	Rat (Wistar)	PS microplastics, ~0.5 μm; dose not reported (oral)	8 weeks (chronic)	Myocardial histopathology, cardiomyocyte apoptosis, cardiac injury biomarkers (troponin I, CK-MB)	PS microplastic exposure activated pro-fibrotic Wnt/β-catenin signaling in the rat heart, leading to interstitial cardiac fibrosis and increased cardiomyocyte apoptosis. Treated rats exhibited elevated cardiac injury biomarkers and oxidative stress, implicating microplastics as a trigger for adverse cardiac remodeling.
Zhao J, Gomes D, Jin L et al. [68]	Mouse (ICR)	PS nanoplastics; size not specified (nanoscale); 0.5 and 5 μm aggregates; 0.1 and 1.0 μg/mL in drinking water	5 months (chronic)	Metabolic indices, fasting blood glucose, and insulin sensitivity	Chronic ingestion of low-dose PS micro/nanoplastics caused increased adiposity and weight gain in mice, along with elevated blood glucose. These changes suggest microplastic exposure can promote a cardiometabolic profile that may accelerate vascular aging and elevate cardiovascular risk.
Lin P, Tong X, Xue F et al. [69]	Mouse (Kunming)	PS nanoplastics; ~100 nm; 5 mg/kg (oral)	60 days (chronic)	Myocardial ultrastructure, ROS levels in the heart, fibrosis markers, TGF-β1/Smad pathway activation	Oral PS nanoplastics led to myocardial structural abnormalities with elevated ROS in cardiac tissue. Mice showed activation of TGF-β1/Smad signaling and increased collagen deposition in the myocardium, culminating in fibrotic cardiac remodeling. This indicates microplastics can provoke oxidative-stress–driven cardiac fibrosis and impair heart function.
Yin K, Lu H, Zhang Y et al. [70]	Chicken (Gallus domesticus)	PS microplastics, ~5 μm; 1, 10, 100 mg/L in drinking water	4 weeks (chronic)	Cerebrovascular injury (intracerebral hemorrhage incidence), brain inflammation (IL-1β), neuronal pyroptosis (caspase-1, GSDMD)	Oral microplastic exposure in chickens precipitated intracerebral hemorrhages accompanied by mitochondrial dysfunction in brain tissue. Affected birds exhibited intense neuroinflammation and pyroptotic cell death in the brain, linking microplastics to cerebrovascular injury and stroke risk.
Zhang Y, Yin K, Wang D et al. [71]	Chicken (Gallus domesticus)	PS microplastics, ~5 μm; 1, 10, 100 mg/L in drinking water	4 weeks (chronic)	Cardiac inflammation (myocardial IL-6, TNFα), pyroptosis in heart (NLRP3 inflammasome activation, caspase-1)	Chronic PS microplastic intake induced cardiotoxic effects in chickens, including myocarditis and cardiomyocyte pyroptosis. Hearts showed increased pro-inflammatory cytokines and NLRP3 inflammasome activation, leading to pyroptotic cell death. This ROS-driven inflammatory injury to the heart highlights microplastics as a trigger for pathological cardiac inflammation.
Zhang Y, Wang D, Yin K et al. [72]	Bird (Domestic fowl)	PS microplastics, ~5 μm; 1, 10, 100 mg/L in drinking water	4 weeks (chronic)	Cardiac development, ER stress markers (GRP78, CHOP), and autophagy flux in myocardium	Microplastic exposure in developing birds led to myocardial dysplasia and structural abnormalities in the heart. The mechanism involved pronounced endoplasmic reticulum stress and altered autophagic pathways in cardiac tissue, suggesting that microplastics impair protein homeostasis in cardiomyocytes and disrupt normal heart development.
Zhang T, Yang S, Ge Y et al. [73]	Mouse (ICR)	PS nanoplastics, ~40 nm; inhalation at ~16, 40, 100 µg/day	1, 4, or 12 weeks (acute to subchronic)	Cardiac function, myocardial injury biomarkers (LDH, CK-MB), oxidative stress (MDA, SOD levels), cardiac histopathology (inflammation, fibrosis)	Respiratory exposure to nano-PS caused dose- and time-dependent cardiotoxic effects. Acute exposure provoked intense cardiac inflammation and immune cell infiltration, while subacute/subchronic exposure led to reduced systolic function and structural heart damage. Mice showed elevated cardiac injury enzymes and oxidative stress, with evidence of mitochondrial damage in cardiomyocytes. Overall, inhaled nanoplastics induced myocardial injury and accelerated cardiac tissue aging changes.
Cell Line (in vitro)
Saugat Shiwakoti, Ko JY, Gong DS et al. [74]	Endothelial cells (PCAEC, porcine coronary artery)	PS nanoplastics, ~25 nm	0.1, 1, 10 µg/mL; 24 h exposure	Cellular senescence markers (SA-β-gal activity, p16, p21, p53 levels), nitric oxide bioavailability	PS nanoparticle exposure caused endothelial cells to acquire aging features. Treated PCAECs showed increased senescence-associated β-galactosidase staining and upregulated cyclin-dependent kinase inhibitors p16, p21, and p53. Endothelial NO production was impaired, indicating functional endothelial dysfunction alongside the senescence phenotype.
Bikalpa Dhakal, Saugat Shiwakoti, Park EY et al. [75]	Endothelial cells + SGLT2 inhibitor (porcine coronary artery)	PS nanoplastics, ~25 nm	5 and 10 µg/mL; 24 h (± empagliflozin)	Endothelial senescence (SA-β-gal), ROS generation, eNOS expression, and cell viability	Low-dose PS NPs induced marked premature senescence and dysfunction in endothelial cells. Co-treatment with an SGLT2 inhibitor blunted these effects, reducing oxidative stress and senescent cell burden. This demonstrates that NP-induced endothelial aging is mechanistically linked to SGLT2, and blocking this pathway can ameliorate microplastic-induced vascular aging.
Basini G, Stefano Grolli, Bertini S et al. [76]	Endothelial cells (AOC line, porcine aorta)	PS nanoplastics, ~100 nm	5, 25, 75 µg/mL; 24 h exposure	Cell metabolic activity (MTT assay), redox status (intracellular ROS), and angiogenic factor (VEGF) secretion	High concentrations of PS nanoplastics led to dose-dependent cytotoxicity in aortic endothelial cells. Nanoplastic-treated cells showed reduced metabolic activity and a significant increase in oxidative stress. Secretion of VEGF was altered, indicating that microplastics can impair endothelial angiogenic signaling and viability at higher doses.
Vlacil AK, Bänfer S, Jacob R et al. [50]	Microvascular endothelial cells (murine heart)	PS microplastics, ~1 µm	0.54 ng/mL, 54 ng/mL, 5.4 µg/mL; 6 h + 18 h (24 h total)	Endothelial activation, monocyte adhesion assay (THP-1 binding)	Exposure to 1 µm PS particles activated mouse cardiac endothelial cells, evidenced by upregulation of adhesion molecules and a pro-inflammatory phenotype. Treated endothelial monolayers showed significantly increased adhesion of monocytes, indicating microplastics promote endothelial dysfunction that favors leukocyte recruitment—an early step in vascular inflammation and atherogenesis.
Roshanzadeh A, Oyunbaatar NE, Ganjbakhsh SE et al. [77]	Cardiomyocytes (neonatal rat heart cells)	PS nanoplastics, ~50 nm	25 μg/mL	Contractile function, calcium handling (L-type Ca2+ channel current)	Neonatal cardiomyocytes exposed to PS nanoplastics exhibited weakened, synchronized contractions. Nanoplastics readily internalized into cardiomyocytes and inhibited L-type Ca2+ channels, leading to reduced calcium influx and contraction force. This suggests microplastics can directly disturb cardiac electrophysiology and muscle function, potentially contributing to arrhythmias or heart failure with prolonged exposure.
Barshtein G, Livshits L, Shvartsman LD et al. [78]	Red blood cells + endothelium (human)	PS nanoplastics, 50–250 nm	50 and 100 µg/mL; 2 h co-incubation	Erythrocyte aggregation index, RBC–endothelial adhesion	Polystyrene nanoparticles promoted abnormal clumping of human erythrocytes and their adhesion to endothelial cell layers. Smaller nanoplastics had a more pronounced effect than larger ones, causing up to a 2.5-fold increase in RBC aggregation. These findings highlight a potential mechanism for microplastics to induce microvascular occlusions or thrombosis by enhancing red cell aggregation and vascular sticking.
Florance I, Chandrasekaran N et al. [79]	Monocyte-macrophage cells (THP-1, human)	Mixed PS micro/nanoplastics (20 nm–10 µm)	10–100 µg/mL; 24 h exposure	Inflammasome activation, IL-1β and IL-18 cytokine release	Across a panel of plastic particles, THP-1 macrophage-like cells responded to micro/nanoplastics with significant NLRP3 inflammasome activation. This led to the release of IL-1β, IL-18, and other inflammatory cytokines, indicating that microplastics can directly trigger innate immune pathways. Such macrophage activation within vessels can exacerbate endothelial inflammation and contribute to vascular aging and plaque instability.

highlights key experimental models used to study microplastic impacts on the vascular system, along with major findings and their implications for human health.

Most toxicological data on microplastics comes from studies performed in vitro and on animals; recent human studies have begun to validate direct correlations between the levels of MP in the body and adverse cardiovascular outcomes. Exposure duration in experimental models greatly affects vascular outcomes. Acute exposures (≤14 days) cause acute oxidative and inflammatory alterations, whereas chronic exposures (≥4 weeks) cause prolonged vascular damage, myocardial remodeling, and atherosclerotic development [Table 1]. Research indicates that elevated microplastic levels are associated with an increased risk of heart disease, mediated by hypertension, systemic inflammation, endothelial dysfunction, and increased thrombotic events. This suggests that microplastics may contribute to premature vascular aging and circulatory disorders.

Table 2. Summary of Human Studies for Vascular Effects of Microplastics.

Author(s)	Study Design	Population	MP Exposure	Cardiovascular Outcomes	Vascular Aging Indicators	Key Findings
Marfella R., Prattichizzo F., Sardu C. et al. [80]	Prospective cohort	Patients with carotid atherosclerotic plaques (n = 257)	Carotid plaque (pyrolysis-GC/MS, mostly polyethylene)	3-year incidence of MI, stroke, and death	Carotid plaque burden (atherosclerosis)	Microplastics were found in 58% of plaques. A 4.5-fold higher CV event risk
Yang Y., Zhang F., Jiang Z. et al. [24]	Cross-sectional	ACS patients vs. controls (n = 101)	Blood MPs via pyrolysis-GC/MS (PE, PVC, PS)	ACS severity, SYNTAX score	Coronary complexity (indirect)	Higher MP levels were seen in myocardial infarction patients than with unstable angina and controls. Levels of MPs were correlated with inflammation.
Wang S., Yan K., Dong Y. et al. [81]	Cross-sectional + animal study	Hypertensive vs. normotensive adults	MPs in feces	Hypertension, BP	None in humans	Higher MP levels were seen in hypertensive patients. The animal model confirmed CV remodeling.
Geppner L., Grammatidis S., Wilfing H. et al. [82]	Single-arm intervention	Healthy adults (n = 8)	Plastic-free diet (water intake from tap)	Brachial BP (pre vs. post)	None	Reduced systolic/diastolic BP after plastic-reduction, especially in females.
Hua K., Yang X. et al. [83]	Pilot tissue analysis	Cardiac surgery patients (n = 15)	Heart tissue and blood MPs (laser IR imaging)	None directly measured	None	MPs were detected in most heart tissues and circulating blood pre-/post-op
Wang T., Yi Z., Liu X. et al. [84]	Cross-sectional	Thrombotic event patients (n = 30)	Excised thrombi (10 polymer types)	Stroke severity, D-dimer levels	Thrombotic burden (indirect)	80% of thrombi had MPs. Higher MP levels were linked to severe stroke, coagulopathy.
Lee D-W., Jung J., Park S. et al. [85]	Cross-sectional	Healthy adults (n = 36)	Blood MPs via μ-FTIR (4.2 particles/mL avg)	aPTT, fibrinogen, CRP, platelets	None	Higher MPs are linked to altered coagulation and CRP. MP levels were also linked to plastic food use.

summarizes current human studies that evaluate microplastic exposure, addressing cardiovascular and vascular health effects.

4. Molecular Insights: Signaling Pathways Affected by Microplastics in Vascular Cells

4.1. Inflammatory Activation and Immune Signaling

Endothelial inflammation and the infiltration of immune cells are emerging as novel mechanisms by which microplastics have adverse affect. Research by Vlacil et al. demonstrated that exposure of endothelial cells to 1 µm polystyrene particles results in significant activation of nuclear factor kappa-B (NF-κB). This activation process enhances the expression of VCAM-1 and ICAM-1 adhesion molecules, facilitating leukocyte adherence. Upon stimulation, monocytes increase their synthesis of inflammatory cytokines, including interleukin-6 (IL-6), TNF-α, and several others. Researchers observed increased inflammatory cytokine signals and adhesion molecules in mouse aortic endothelial cells upon injection of mice with identical MPs. Endothelial cells respond via inflammatory pathways, including NF-κB and MAPK signaling, to generate expression of inflammatory proteins [50].

Prolonged exposure to microplastics at low concentrations results in a chronic inflammatory state inside vascular tissues. Research involving mice that ingested MP for a longer duration demonstrates a sustained increase in vascular adhesion molecules and ongoing infiltration of inflammation-related monocytes. Extended NF-κB signaling pathways remain unregulated during the monitoring period. Endothelial cells and native vascular macrophages experience adverse effects as a result. The macrophages ingest MPs while concurrently entering a pro-inflammatory state [86]. Toll-like receptor pathways are triggered upon the entry of nanoparticles into macrophages, leading to their accumulation inside these cells. The activation process leads to the generation of interleukin-1 beta (IL-1β) and interleukin-18, along with the assembly of the NLRP3 inflammasome, which induces inflammatory pyroptosis. The interaction between MPs triggers innate immune signaling pathways in vascular tissues, functioning similarly to responses to pathogens and exposure to particulate air pollution. NF-κB, in conjunction with MAPKs and inflammasomes, activates to coordinate the first and prolonged phases of the immuno-inflammatory response [86,87] [Figure 3].

4.2. Endothelial Dysfunction and Barrier Integrity

Interaction between human cells with MPs and NPs impairs their functionality, leading to reduced barrier integrity. The permeability of monolayers increases when the endothelium interacts with nanoparticles, probably due to the attenuation of tight junction proteins. Polystyrene nanoparticles induce a decrease in occludin levels and decrease transendothelial electrical resistance in brain microvascular endothelial cells, consequently compromising tight junction integrity [88,89,90]. Laboratory tests indicate that the rupture of endothelial cells results in necroptosis and triggers an inflammatory response [91,92,93]. Endothelial dysfunction demonstrates decreased availability and synthesis of protective endothelial signaling molecules. Current information indicates that MPs adversely influence regulatory molecules by diminishing endothelial nitric oxide signaling via endothelial nitric oxide synthase and elevating endothelin-1 levels [94,95].

Research has demonstrated that rat exposure to microplastic aerosols causes blood pressure elevation, together with reduced vasodilatory responses that reflect endothelial damage [96]. Prolonged exposure to microplastics induces endothelial cells to elevate the expression of VCAM-1 and ICAM-1 adhesion receptors, hence indicating endothelial dysfunction and atherogenic activation [50]. Prolonged exposure of the endothelium lining to microparticles leads to damage that decreases the regenerative capacity of cells. Research findings indicate that NPs accelerate endothelial cell aging by elevating p53/p21 signaling alongside senescence-associated β-galactosidase activity, hence reducing cellular proliferation [74]. The characteristics of vascular dysfunction increase as the senescent phenotype restricts barrier repair mechanisms and reduces nitric oxide synthesis.

4.3. Vascular Smooth Muscle Cell and Foam Cell Pathways

Microplastics within the vascular walls influence vascular smooth muscle cells and infiltrating immune cells, which together alter arterial structure. They change the VSMCs’ phenotype, causing them to go from a contractile to an inflammatory and synthetic state. Polystyrene microplastics at a concentration of 50 µg/mL result in a reduction in contractile marker expression in vascular smooth muscle cells, while concurrently increasing the expression of synthetic and inflammatory genes. The phenotypic change in cells depends on the small RNA molecule tiRNA-Glu-CTC, which precisely triggers targeted gene expression [42,97]. Research demonstrates that MPs could contribute to the progression of vascular calcification. The brief exposure of rats to microplastics resulted in minimal vascular calcification, but the ingestion of microplastics intensified calcification progression in pro-calcific mice models treated with vitamin D3 and nicotine. This indicates that MPs can induce osteogenic signals under specific situations. The inflammatory response and potential intestinal dysbiosis, which can result in systemic inflammation, are processes that can happen when MPs affect the vessel wall [86].

The vascular microenvironment facilitates the interaction of microparticles with circulating monocytes and macrophages, thus influencing their role in foam cell generation, a crucial process in the development of atherosclerosis. Research indicates that nanoparticles coated with anionic surfactants promote significant lipid accumulation in cellular macrophages, resulting in the formation of lipid-laden foam cells. Acute mitochondrial oxidative stress induced by these nanoparticles results in excessive lipid accumulation in lysosomes, impairing their lipid clearance function [98]. This process replicates the mechanism by which oxidized LDL induces atherosclerosis via the absorption of altered lipid and particle components by macrophage scavenger receptors CD36 and MARCO [99]. Research conducted on hyperlipidemic ApoE⁻/⁻ mice confirmed that circulating nanoparticles enhance macrophage MARCO receptor expression, resulting in increased cholesterol ester buildup and accelerated plaque formation [66]. The interaction of MPs, foam cells, and VSMCs determines plaque formation. Prolonged intercellular contacts lead to the formation of vascular lesions. Prolonged exposure to MPs in the murine population has detrimental effects, including arterial stiffness, increased plaque accumulation, and alterations in plasma lipids characterized by higher LDL and reduced HDL levels [100].

4.4. Cell Death and Stress Pathways

Cellular stress responses occur during acute microplastic exposure, leading to various forms of vascular cell death. A significant concentration of internalized nanoparticles induces death in endothelial cells via mitochondrial pathways, leading to the release of cytochrome c and activation of caspases. The process of endothelium apoptosis demonstrates elevated p53 protein expression, particularly with exposure to greater doses or longer durations [74]. Studies using polystyrene MPs on animals’ cardiomyocytes alongside vascular cells demonstrated increased apoptosis through enhanced TUNEL-positive cell counts as well as elevated caspase-3 levels [77]. Through activation of the NLRP3 inflammasome, MPs can trigger pyroptosis, which represents an inflammatory cell death form that results from gasdermin D pore formation. The administration of MP in rodent models results in increased levels of IL-1β and IL-18 in cardiac and vascular tissues, indicating inflammasome activation and pyroptosis-mediated damage to vascular cells [101]. Research confirmed the NF-κB/NLRP3/GSDMD axis by showing that NF-κB activates gasdermin D, leading to pyroptosis and subsequent heart damage caused by MP [71]. Conversely, researchers have noted that fine particle air pollution employs the same mechanisms for apoptosis and pyroptosis to activate these processes in endothelial cells when examining their structural responses to hazardous particulate matter [95].

The cellular recycling process known as autophagy exhibits alterations when cells interact with microplastic particles. The initial phase of restricted autophagy functions protectively by attempting to eliminate NP particles and defective organelles. Endothelial cells form autophagosomes when exposed to 100 nm nanoparticles to contain foreign substances. The autophagy flow is inhibited by both MPs and NPs, resulting in the accumulation of autophagosomes and increased cellular stress levels [102]. In HUVECs, 100 nm nanoparticles have been shown to disrupt lysosomal degradation, perhaps overloading the system or inducing lysosomal injury, which leads to delayed autophagy and promotes cell death [102]. Extended exposure of endothelial cells to elevated quantities of microplastics results in necrotic cell death rather than survival, as indicated by the study conducted on endothelial cell models [103]. The persistent exposure to stressors can deplete autophagy protective systems, leading to cell death via necrosis or necroptosis.

The RIPK3/MLKL signaling pathway induces necroptosis in brain endothelial cells upon exposure to nanoparticles, accompanied by NF-κB activation and reactive oxygen species production [93]. Endothelial cells undergo irreversible cell growth arrest characterized by cellular senescence as a result of MP exposure. Senescent cells preserve their metabolic processes with pro-inflammatory activities, referred to as the senescence-associated secretory phenotype. Blood vessels with elevated levels of these particles have reduced healing capabilities, resulting in chronic inflammation. Research indicates that NP exposure in porcine origin arteries elevates the metabolic sensor SGLT2, resulting in the upregulation of senescence markers [75]. Research suggests that SGLT2 inhibition mitigates cellular senescence, revealing a compelling mechanism by which microplastics may accelerate vascular aging via metabolic disruptions [75].

4.5. Acute vs. Chronic Exposure: Differences in Pathway Activation

Cellular biological responses exhibit significant differences between acute high-dose and prolonged low-dose exposure to MPs. Acute exposure lasting hours to days triggers immediate stress responses by elevating reactive oxygen species and inflammatory cytokines, resulting in cellular death at extremely high concentrations. Endothelial cells exhibit susceptibility to apoptosis or necrosis when subjected to elevated concentrations of MPs at 100 µg/mL, as indicated by polystyrene MPs [104]. Cells subjected to brief exposure to MP in vitro rapidly activate NF-κB signaling alongside inflammasome pathways, leading to the prompt release of IL-1β and IL-18 [101]. In vivo, a short exposure to microplastics might induce acute inflammation, as evidenced by mice intraperitoneally administered with microplastics, which exhibited increased levels of aortic IL-6 and TNF-α within days [50]. Although excessive MP dosages (40–400 μg/L) can cause cellular damage rapidly, acute toxicity can also include transitory oxidative stress, in which cells temporarily activate antioxidant defenses via the Nrf2 pathway [105].

Conversely, prolonged exposure to MPs, lasting weeks to months, often leads to more nuanced alterations in vascular cells. Prolonged low-level MP exposure may not result in rapid cellular death but induces accumulated dysregulation. Chronic inflammation often occurs; even at minimal dosages, the continuous presence of MPs maintains endothelial cells and macrophages in an activated condition, fostering the ongoing release of cytokines and adhesion molecules [103]. This may lead to pathological remodeling of blood arteries, characterized by intimal thickening and plaque formation. A 12-week study in mice showed that prolonged consumption of microplastics intensified arterial lesions and correlated with extensive alterations in vascular gene expression patterns, impacting pathways linked with cell proliferation, metabolism, and fibrosis within the cardiovascular system [75]. In contrast to the initial surge in ROS, prolonged exposure may create a novel homeostatic set-point marked by increased levels of endogenous antioxidants with persistent mild oxidative stress. This extended oxidative environment may result in DNA damage and cellular senescence in vascular cells, similar to findings of nanoparticles triggering endothelial senescence with repeated exposure [74].

5. Evidence of Adaptation to Microplastic Exposure

The human body has shown indications of adaptability to low-level microplastic exposure, especially via gut microbiome processes. Research has revealed plastic-degrading genes in human gut microbial communities, indicating that these microbiomes may digest microplastics, possibly alleviating their detrimental effects [106]. Particular bacterial taxa, including Roseburia, Clostridium, and Prevotella, have significant correlations with microplastic biodegradation. Furthermore, natural clearing systems play a role in the reduction in microplastics. The intestinal and respiratory epithelia serve as physical barriers that inhibit the entry of bigger microplastics into the body, while smaller particles (up to 5 µm) may still breach these defenses [107]. Moreover, internal organs such as the liver and kidneys contribute to the filtration of microplastics from the bloodstream, but the efficacy of these mechanisms is not well understood [108]. Microplastic exposure may beneficially modulate immune system responses in certain contexts, such as by enhancing the production of specific cytokines crucial for immune regulation and affecting the gut microbiota to generate short-chain fatty acids, which may promote anti-inflammatory responses [106,109]. However, these immune-modulating effects are still at the preclinical stage and require more examination, particularly in light of conflicting evidence indicating pro-inflammatory responses have also been seen [110,111]. Population studies investigating the health consequences of microplastics provide inconsistent findings; human research often suggests no negative repercussions, underscoring the resilience and adaptability of the gut microbiome in preserving microbial stability when exposed [106]. In contrast, animal studies, especially those using mouse models, often indicate substantial alterations in gut microbiota composition, intestinal barrier integrity, and immune responses, highlighting the intricate and context-dependent characteristics of these interactions [112]. Furthermore, correlations between microplastic exposure and health outcomes, including inflammation, oxidative stress, and immune dysfunction, are not uniformly reported across studies, highlighting existing research limitations such as methodological inconsistencies in the detection and quantification of microplastics, varied exposure conditions, and insufficient understanding of the long-term effects of sustained exposure [20,113,114]. Consequently, while evidence of human adaptability to microplastics is present, thorough assessments of long-term health effects are essential.

6. Future Therapeutic and Policy Interventions

Integrating biomedical treatments with environmental policies via multidisciplinary approaches is essential to mitigate microplastic-induced vascular aging. Future medical research should emphasize and address the inflammatory responses and oxidative stress caused by microplastics in the body. Therapies containing antioxidants are being studied to counter the reactive oxygen species that develop from microplastic exposure. Several dietary antioxidants like lycopene, alongside citric acid and chlorella, show potential at reversing microplastic-caused fibrosis and tissue damage in animal studies [113]. Studies suggest that antioxidants and NAD⁺-enhancing substances can help reduce cellular aging responses, together with endothelial dysfunction triggered by microplastics [109].

Gut microbiota modulation shows potential as an effective strategy to mitigate the effects of microplastics. Microplastics disrupt the intestinal microbiome, compromising gut barriers and facilitating systemic inflammation. Prebiotic fiber treatments alongside probiotic interventions can strengthen the gut barrier to reduce the movement of lipopolysaccharide, along with microplastic particles, through the bloodstream. Specific probiotic administration in mice has shown that it helps reduce intestinal permeability and prevents dysbiosis-driven aortic atherosclerosis [115]. Fecal microbiota transplants or custom synbiotics could become useful tools in the future for restoring microbial balance among individuals who are chronically exposed to microplastics. Research must focus on creating methods for the clinical observation and monitoring of exposure to microplastics as part of intervention strategies. Advancements in analytical techniques now create the possibility for future widespread determination of microplastic exposure in individuals, along with their risk markers. Polymer particles have been measured in human blood and arterial plaques in recent studies [85]. This suggests that clinical laboratories may soon use microplastic analysis as part of exposure biomonitoring. In an approach similar to heavy metal screening, non-invasive tests can function as advanced alert systems that identify significant exposure levels. Additional biomarker assessment of inflammatory markers and endothelial dysfunction alongside vascular health checks may help facilitate treatment in individuals displaying high microplastic levels. Researchers can determine exposure threshold limits and identify sensitive populations through clinical data over time.

Public health and policy actions must accompany biomedical strategies to reduce microplastic exposure at the source. Several nations have banned primary microplastics, like cosmetic microbeads, and regulated others. The US, Canada, and UK have prohibited plastic microbeads in rinse-off personal care items, while California requires microplastic testing of drinking water [116]. France requires washing machine filters to trap microfiber contamination, and Norway bans non-biodegradable single-use plastics and limits microplastic usage in agriculture and sports. The recently launched UN Plastics Treaty discussions might limit plastic manufacturing and waste globally, reducing microplastics. Policies should also support studies into the efficacy of these measures, as existing regulations have only just begun to be implemented, and their effects on microplastic prevalence and health outcomes are unclear [116].

Our understanding of how microplastics cause vascular aging is poor, despite growing concern. To determine actual dose–response relationships, long-term studies on low-level, chronic exposure are needed. To understand microplastic-induced vascular damage, immunological activation, ER stress, and metabolic reprogramming must be studied alongside oxidative stress. Studies to separate particles from their adsorbed toxins are needed to determine microplastics’ involvement as carriers of co-pollutants such as PAHs and heavy metals. No longitudinal studies have connected microplastic exposure to cardiovascular outcomes, underlining the need for strong biomarkers and large-scale population investigations. Without uniform sample, detection, and reporting techniques, cross-study comparisons are difficult. Finally, studies should examine if biological clearance, enzymatic breakdown, or nutritional treatments can reduce microplastic deposition in the body.

7. Conclusions

Microplastics and nanoplastics are ubiquitous and enter the body through food, inhalation, and skin contact, prompting worries about their long-term effects on vascular health. MPs cause vascular aging through oxidative stress, chronic inflammation, endothelial dysfunction, and cellular senescence. Microplastic exposure triggers NF-κB, NLRP3 inflammasome, and redox-sensitive signaling cascades, leading to vascular remodeling, smooth muscle changes, and atherogenic transformation. These consequences may be understood using animal and cellular models, but interspecies variations and limited human data leave translational gaps. New discoveries on adaptive responses, such as gut microbiota-mediated MP breakdown and immunological regulation, show a complicated relationship between microplastic exposure and human physiology that needs more study. Microplastic exposure is a novel, understudied vascular aging connection. To protect cardiovascular health against plastic pollution, mechanistic research, population-level research, and environmental policy reform are needed.