Introduction

Cardiovascular disorders and environmental contamination from microplastics (MPs) are two major challenges within modern society [1, 2]. Currently, our understanding of the interrelationship between these two phenomena is limited [3]. Contemporary evidence points towards an increasing bioaccumulation of micro- and nano-plastics (MNPs) in humans, leading to increased disease and dysfunction within multiple organ systems, thereby presenting a threat to global public health [3, 4]. However, a lack of research and evidence synthesis to date currently leaves clinicians with insufficient data to guide the management of patients with MNP-associated disease and dysfunction.

In 2019, the World Health Organization (WHO) published a report entitled ‘Microplastics in Drinking-Water’, which minimised the significance of MNPs in drinking water in relation to their impact on human health [5]. The first report of MNPs in the human bloodstream was published in the same year. Since this time, the assertation that there is “no evidence to indicate a human health concern” [5], is increasingly being challenged by new studies. Once MNPs enter the human body, by means of inhalation, ingestion, or dermal absorption, they can cross biological barriers, leading to systemic exposure and bioaccumulation in vital organs and tissues [4, 6,7,8]. The ability of MNPs to influence inflammatory [6, 9], metabolic [6, 10], and endocrine pathways [11], in addition to their cytotoxic [12, 13], immunotoxic [6, 14], and genotoxic [12, 13] effects, suggests their implication in a number of disease processes. The discrepancy between the WHO report and current literature emphasises the need for urgent re-evaluation of the health impact of MNPs.

The definition of MNPs is a crucial starting point for this re-evaluation. A lack of consensus in literature elicits conflicts within public policy, legislation, research and medicine, compounding pre-existing challenges in monitoring and mitigating the impacts of MNPs. Moreover, the characteristics of these MNPs, such as their functionalisation, surface characteristics, shape, additives, pigmentation and polymer type, are essential in understanding their behaviour and impact on human health. However, these characteristics are yet to be considered in the literature, with most studies focusing only on particle size.

Cardiovascular disease remains a leading cause of morbidity and mortality globally, with data demonstrating that despite advances in recent decades, the mortality rate may be beginning to rise [1]. This concerning trend necessitates urgent research into the mechanisms surrounding the aetiology and progression of diseases relating to vascular pathologies, heart failure, and congenital and electrical abnormalities. This scoping review aims to systematically explore and summarise the literature surrounding MNPs in the human cardiovascular system and their pathological consequences, and explore the methodologies used in their detection and analysis, guided by the following research questions:

RQ 1. How are MNPs defined within the current cardiovascular literature?

RQ 2. What are the characteristics of plastics which have been found within human cardiovascular systems?

RQ 3. What methodology has been utilised to date to characterise plastics within human cardiovascular systems?

RQ 4. What are the pathophysiological considerations which have been explored regarding the presence of plastic in human cardiovascular systems?

For the purpose of this review, a broad definition of the term ‘cardiovascular system’ will be employed, inclusive of the heart, blood vessels, blood, and the components (e.g. immune cells) commonly found within human blood. While other reviews have previously provided broad insights into the potential health implications of MPs, this scoping review, through a rigorous and systematic interrogation of existing literature, attempts to solidify the field of knowledge surrounding MNPs and the cardiovascular system specifically, raise awareness of the scale of this emerging issue, and lay the foundation for further research which may assist in the development of health policies and clinical practice guidelines.

Methods

Protocol and registration

An a priori protocol was developed, informed by the recommendations of Arksey and O’Malley [15], the Joanna Briggs Institute (JBI) [16], and the PRISMA extension for scoping reviews reporting guidance (PRISMA-ScR). This protocol was published on the Open Science Framework (https://osf.io/w9hr5) on March 8th 2024. This review was conducted in accordance with the ethical principles set forth in the Declaration of Helsinki.

Eligibility criteria

A pre-determined eligibility criteria was developed, informed by the population (human), concept (microplastics or nanoplastics and their effects) and context (cardiovascular system). Any studies investigating the presence of MNPs within the human cardiovascular system, or their effects on human cardiovascular outcomes or on relevant human cells lines, were included. Pre-determined definitions were developed and outlined within the a priori protocol after careful interrogation of the existing literature. For clarity, plastics were defined as a synthetic or semi-synthetic material comprising organic polymers from plant extracts or fossil fuels. The term ‘cardiovascular system’ was defined simply as the heart, blood, and associated vessels. To ensure a broad and thorough scope of the literature was undertaken, all research methodologies were included except for abstracts, reviews, pre-prints, conference proceedings, poster presentations, and editorials. No date restrictions were applied to the search strategy.

Search strategy

A search strategy was developed utilising a three-step approach originally proposed by Arksey and O’Malley [15] and further outlined by the JBI. Firstly, a pilot search of PubMed and Google Scholar was undertaken on January 19th 2024. Secondly, results were reviewed to identify additional search terms, with the final search strategy being translated for additional search engines with the assistance of a validated search engine translation software (Systematic Review Accelerator [SRA] Polyglot) [17] (Appendix 1). The final search was executed on November 27th 2024. An additional search for grey literature was undertaken utilising Research Rabbit [18], TERA Farmer [19], and Perplexity [20].

Information sources

Five databases (PubMed, EMBASE, CINAHL, SCOPUS, and Web of Science) were searched on November 27th 2024. Results from database searches were exported into Endnote X9 [21].

Selection of sources of evidence

Duplicate results were removed utilising automation software (SRA Deduplicator) [22]. Articles were screened by two authors by title and abstract within SRA Screenatron [22]. Full text screening was undertaken within Covidence [23] by two authors with discrepancies resolved by a third author.

Charting of data items

A draft extraction table was developed within Microsoft Excel to align with the aims of the scoping review. This was piloted and refined prior to undertaking full data extraction. Where information was not relevant or not reported, this was recorded for clarity.

Synthesis of results

Data pertaining to definitions was extracted and, where possible, synthesised and visually represented. Similarly, data pertaining to the countries and years of publication was tabulated and visually represented. Studies identifying the presence of plastic in human specimens, and studies evaluating the effects of plastic on cellular viability, uptake, and function, have been tabulated separately.

Results

Selection of sources of evidence

Database searching led to the retrieval of 1188 articles, of which 743 articles were removed via automation within Systematic Review Accelerator and Covidence (Fig. 1). Title and abstract screening of the remaining 445 articles led to the exclusion of a further 375 articles. The full text of 69 out of the 70 identified articles was successfully retrieved and screened with substantial agreement between authors (Cohen’s Kappa = 0.760). This process led to the exclusion of a further 23 articles resulting in 46 articles being included within the review.

Fig. 1
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PRISMA ScR flow diagram.

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Synthesis of results

Of the 46 identified articles, 15 countries were represented, with China (n = 14), Spain (n = 5), the United States of America (n = 4), Italy (n = 4) and India (n = 4) representing over half (67%) of all identified publications (Fig. 2). Only one article was published prior to the WHO report on MPs in drinking water [5] being made publicly available. All articles defined MPs and nanoplastics (NPs) primarily based on the size of the particle (Table 1). Thirteen articles (Table 2) identified the presence of MNPs in venous blood samples, cardiac tissue, thrombi, saphenous veins and atherosclerotic plaques, with implications for all-cause mortality (Fig. 3). Sizes of identified particles varied greatly from 1 to 3000 μm (Fig. 4). The remaining 33 articles were in vitro investigations into the effect of MNPs on human cell lines relating to the cardiovascular system (Table 3). However, a discrepancy exists between the polymers used within in vitro studies and the types (Table 4) and characteristics of polymers that have actually been found in human vascular and cardiac tissue. The limited sensitivity of detection methodologies utilised to date has hindered the identification and characterisation of smaller NPs in human samples. These smaller NPs, as shown through in vitro studies, tend to have more pronounced adverse effects.

Fig. 2
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Details pertaining to country of origin, number of publications per country and year of publication.

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Fig. 3
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Treemap depicting proportion of studies reporting the presence and effect of plastics in human cells or tissues.

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Fig. 4
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Size of plastic organised by sample type.

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Table 1 Details pertaining to definitions of microplastics and nanoplastics listed by date of publication.
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Table 2 Details of articles investigating the presence of MNPs in samples from humans associated with the cardiovascular system.
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Table 3 Details of articles investigating the effect of MNPs on human cell lines and blood samples associated with the cardiovascular system.
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Table 4 Visual display of the variety of plastics currently identified in human samples and utilised within cell line investigations.
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Definitions of microplastics and nanoplastics

Twenty-three (66%) articles provided a description of the term ‘microplastic’, 16 (41%) of the included articles defined the term ‘nanoplastic’, and nine utilised the descriptor MNP (25%). While earlier articles chose to define NPs as particles <100 nm in size [24,25,26,27,28,29], a shift occurred in 2022 whereby articles began to refer to NPs as particles less than 1000 nm in size [30,31,32,33] (Table 1). Increasingly, articles choose to refer to MNPs more generally as particles below 5 mm in size [34,35,36,37,38,39,40] while making specific reference to NPs as particles less than 1000 nm.

Presence of MNPs in atherosclerotic plaques and thrombi and their effects on clotting factors

Two articles were identified analysing the presence of MNPs in atherosclerotic plaques [34, 41] and thrombi [42] respectively (Table 2). Of the 257 patients who completed the 33-month follow up, Marfella et al. [41] identified plastic (polyethylene) in carotid artery atherosclerotic plaques of 150 (58.4%) patients. Additionally, 31 (12.1%) patients had PVC in atherosclerotic plaques. At the 33-month follow up, patients with detectable MNPs had an increased risk of composite outcomes, including myocardial infarction, stroke, or death from any cause, compared to those with MNP-free atherosclerotic plaques [41]. Yang et al. [38] more recently explored the presence of MNPs within the bloodstream of patients with acute coronary syndrome. This study found MNPs within 100% of patients [38]. Similar to Marfella et al. [41], these results found that higher rates of MNP contamination were associated with poorer patient prognosis, as evidenced by higher SYNTAX scores, representing more complex and severe coronary artery atherosclerosis [38].

Two articles were identified which investigated the presence of MNPs in thrombi [35, 42]. Wu et al. published the first study identifying MNPs in human thrombi in 2023, in which they observed a single low density polyethylene particle, alongside other foreign materials including pigments, iron compounds, and metallic oxide particles [42]. Since this time, a larger study has provided further evidence of the widespread presence of MNPs in human thrombi, identifying 384 MNPs in 80% (24/30) of thrombi [35]. Several factors including particle size and functionalisation (e.g. carboxylated or aminated surfaces) have been shown to influence clotting dynamics, with smaller, functional particles demonstrating a greater ability to derange clotting dynamics under low shear environments [30, 43]. Conversely, Arranz et al. found no statistically significant difference in coagulation or platelet function with the addition of 50–130 nm sized polystyrene particles to ex vivo human whole blood at a concentration of 100 μg/mL [44]. While this study provided constant agitation, these in vitro conditions do not account for biochemical and biomechanical factors, such as shear stress, which influence clotting dynamics.

Vascular tissue, endothelial cells and smooth muscle cells

A variety of polymer types have been reported within cardiac tissue obtained during open heart surgery and saphenous vein tissue, with significant variance in quantity per gram, shape and size [45, 46] (Table 2). When investigating the effect of MNPs on endothelial cells, identified articles commonly utilised human umbilical vein endothelial cells (HUVEC) [27, 28, 47,48,49] or vascular endothelial cells (EA.hy926) [50] (Table 3). Additionally, a single article by Lomonaco et al. [36] was identified, investigating the effects of polystyrene and polyethylene (both high and low density) on human coronary artery smooth muscle cells [36]. While Lu et al. [47] found little evidence of deleterious effects following exposure of HUVEC cells to 1 µm spheres, articles utilising smaller particle sizes found polystyrene MNPs to decrease cell viability and increase autophagy [48]. In particular, functionalised polystyrene particles were found to increase oxidative stress and lactate dehydrogenase (LDH), and induce mitochondrial damage, resulting in an 82% decrease in ATP production [27]. Similarly, aged MNPs significantly increased IL-6 and TNF, indicating increased inflammatory processes [36]. It is yet to be determined whether the increase in endothelial leakiness [28, 50] increases MNP interaction with vascular smooth muscle.

Genotoxic effects

The exposure of polystyrene to peripheral blood mononuclear cells was shown to induce micronucleation and damage [25, 51]. While Ballesteros et al. [25] reported no DNA damage associated with 0.04 to 0.1 µm polystyrene NP exposure, Sarma et al. [52], utilising a particle size of 50 nm, demonstrated DNA damage and genomic instability. Dailianis et al. [53] demonstrated that exposure of low-density polyethylene to ultraviolet rays was associated with higher cytotoxicity and genotoxicity. Finally, Li et al. [54] identified 523 differentially expressed genes in response to polystyrene exposure. These genes are involved in processes such as cell development, mitochondrial and lysosomal function, and the downregulation of key pluripotency markers associated with reduced stem cell renewal efficiency.

Discussion

Overview

This systematic scoping review demonstrates that research into the presence and effect of MNPs in the human cardiovascular system has rapidly increased since 2019. While inconsistencies exist in the definition of MNPs in the early literature base, a consistent approach of defining MPs as particles less than 5 mm and NPs as less than 1000 nm in size has emerged since August 2023 (Table 1). The majority of included studies utilised in vitro experimental designs with human samples and cell lines. The findings of the 13 identified articles which investigated MNPs in human tissue are alarming and warrant concern from public health authorities. Of particular note is a lack of research into the presence of MNPs in human samples from low socioeconomic countries, especially those in the Pacific, which are economically and culturally tied to an ocean facing increasing contamination by MNPs. Taken together, the findings of research to date demonstrating the genotoxic, cytotoxic, immunotoxic and neurotoxic effects of MNPs, in addition to their deleterious effects on cellular metabolism and inflammatory effects, raise significant concerns for their role in a range of cardiovascular pathologies including atherosclerosis, cardiomyopathies, electrical and congenital abnormalities, and infective pathologies.

The role of MNPs in atherosclerosis and coronary artery disease

In 2024, Marfella et al. [41] identified MNPs in 58.4% of atherosclerotic plaques, demonstrating that individuals with MNP-associated atherosclerosis had a higher rate of myocardial infarction, stroke, or death at 34-month follow up. Additionally, Yang et al. [38] identified a positive correlation between blood MP concentrations and coronary lesion complexity, as quantified by the SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score. This study identified that acute coronary syndrome patients, particularly those with myocardial infarction, exhibited significantly higher microplastic burden, with associated elevations in inflammatory cytokines such as IL-6 and IL-12p70 [38]. Together, these studies highlight the concern that MNPs may not just play a role in the aetiology of atherosclerosis, but may actually be an important variable in understanding patient prognosis with implications for management decisions.

Investigations employing human and animal cell lines have revealed a multitude of biochemical mechanisms, providing evidence for MNPs in the aetiology and pathophysiology of atherosclerosis, as well as for their significant role in vascular pathologies (Fig. 5). For example, MNPs have been demonstrated to induce endothelial dysfunction, an early stage of atherosclerotic plaque development [55]. Studies utilising 1 µm PS spheres have demonstrated little effect in human umbilical vein endothelial cell lines to date. In contrast, articles utilising smaller and positively charged particles, similar in size to those found within the observational study by Marfella et al. [41], have demonstrated increased ROS and LDH production. Additionally, studies have described damage to mitochondrial membranes, leading to a >82% decrease in mitochondrial ATP production [27], decreased cell viability and impaired angiogenesis, thereby hindering endothelial healing [48, 49]. In addition to endothelial dysfunction, MNPs have deleterious impacts within smooth muscle [56] and lead to decreased levels of high density lipoproteins (HDLs) as well as increased low density lipoproteins (LDLs) [57] and systemic ROS, assisting in the formation of oxy-LDL [58]. Taken together, these results demonstrate the ability of MNPs to lay the foundation for atherosclerotic plaque development.

Fig. 5: Pathways involving MNPs in the aetiology and pathophysiology of atherosclerosis.
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Created with BioRender.com.

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Following their rapid uptake into the cytoplasm of macrophages, NPs provoke lipid aggregation [59], promoting the differentiation of macrophages into foam cells and the development of atherosclerosis [60]. Their continued genotoxic and cytotoxic effect from increased endoplasmic reticulum stress, oxidative stress and disruption to mitochondrial membranes [61] results in apoptosis [62], potentially assisting in the development of a necrotic core, increasing plaque instability [63].

In cases where plaque rupture ensues, MNP contamination deranges the clotting cascade, impacting fibrin polymerisation rates and platelet aggregation. This modulates clot strength and the manner in which the clot adheres to the endothelial wall [64]. Of particular clinical concern is the ability of MNPs to impede the production of endothelium-derived nitric oxide [58, 65], impairing vasodilatory responses to clot formation [66]. Importantly, SGLT2 inhibitors within porcine endothelial models treated with NPs have been shown to upregulate endothelial nitric oxide synthase expression, decrease the formation of ROS, and ultimately inhibit NP-associated endothelial cell senescence [67]. Together, these two studies demonstrate that the production of nitric oxide is perturbed by MNPs, which may impact the delicate haemostatic balance between thrombosis and bleeding. The many pathways through which MNPs may cause cardiovascular disease provide potential pharmacological targets, requiring further exploration into their pervasive effects. Regardless, the involvement of MNPs in atherosclerotic disease provides significant cause for concern, not only in the context of coronary artery disease, but also in peripheral and cerebrovascular pathologies [41].

Valvular disorders, cardiomyopathies, and electrical abnormalities

In addition to vascular diseases, MNPs have been implicated in the dysfunction of cardiomyocytes [68] with potential implications for cardiomyopathies and electrical abnormalities [54, 56, 69] (Fig. 6). For example, the exposure of neonatal ventricular myocytes to NPs has been shown to significantly decrease intracellular Ca2+ levels, in addition to mitochondrial membrane potentials and cellular metabolism, resulting in a reduction in cardiomyocyte contraction forces [69]. Additionally, MNPs in rat models have been shown to induce cardiac fibrosis through activation of the Wnt/β-catenin pathway and cellular apoptosis [70]. Following polystyrene exposure, in vivo rat models have demonstrated increased troponin I and creatine kinase-MB (CK-MB) levels, as well as disruption of mitochondrial mtDNA and cGAS-STING signalling pathways, leading to cardiomyocyte apoptosis [68, 70, 71]. When exposed to MNPs at a concentration equivalent to human exposure, rats demonstrated a marked elevation in cardiac-specific markers and an increase in interventricular septal thickness [72]. This raises considerable concern and highlights a need for urgent research into MNP-associated cardiomyopathies [73].

Fig. 6: Effects of MNP on cardiac tissue.
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Created with BioRender.com.

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Cardiac disorders of infective origins

The rough surface characteristics and size of MNPs found within the human cardiovascular system to date [41] provide an ideal environment to facilitate the adsorption of viruses or bacteria, the development of biofilms, and increased virus survival and infectivity [74,75,76]. MNPs have been shown to promote the infection of cells through the development of a protein corona facilitating a trojan horse mechanism, whereby NP particles shuttle viruses and bacteria into the cytoplasm [77, 78]. Additionally, the presence of MNPs has been shown to inhibit innate immune functions, in particular the actions of macrophages [77, 78]. Beijer et al. [79] demonstrated a dose-related immune response with the largest secretions of IL-1β, IL-8 and TNF-α elicited by polyethylene terephthalate, identified within both human blood and cardiac tissue [26, 46]. As a result, MNPs are likely to play an important role in pathologies such as infective endocarditis, rheumatic heart disease and pericarditis.

Congenital heart abnormalities

Of particular note, research highlighting the presence of MPs in human placentas (including on the fetal side), semen and the meconium of newborns raises important questions surrounding the potential role of MNPs in the aetiology of congenital cardiovascular abnormalities. Research investigating the potential abnormal development of the heart utilising pluripotent stem cells has demonstrated altered atrioventricular valve and cardiomyocyte formation following exposure to polystyrene NPs [80,81,82]. In animal models, NPs have been shown to alter umbilical and placental blood flow [83], with maternal polystyrene NP exposure leading to a 12% reduction in late gestational fetal weight [84]. With more specific reference to the cardiovascular system, maternal MP exposure in rats has also been observed to cause fetal aortic abnormalities [85]. Although current exposure levels are unlikely to cause significant cardiovascular anatomical or physiological abnormalities at birth, there is evidence that MNPs can affect cellular differentiation into cardiomyocytes, disrupt sarcomere organisation, impair contractility, and reduce calcium transients [54]. These findings raise concerns about potential subclinical alterations at birth that may contribute to clinical pathologies later in life [54].

Current gaps in the literature

Despite significant advances in the field of MNPs and cardiovascular health, research is urgently required to assist in the characterisation of MNPs contaminating the human cardiovascular system. Currently, a lack of research exists to appropriately inform animal and cell line research regarding the characteristics of human environmental exposure (Table 4). Without a comprehensive understanding of the types, sizes, characteristics (leachates, surface characteristics, electrical charge, shape, etc.) and concentrations of MNPs within the human cardiovascular system, it is unclear if cell line research currently provides a solid understanding of the effects of MNPs within the general population or in specific populations, such as those investigated by Marfella et al. [41] (carotid endarterectomy) or Yang et al. [38] (acute coronary syndrome). Results of in vitro studies should, therefore, be interpreted with caution until further research characterises the presence of MNPs in humans and explores the long-term effects of their bioaccumulation on disease outcomes through additional in vivo studies which include long-term follow up. To assist with this, researchers moving forward should consider consulting with scientists familiar with the challenges associated with MNP detection and characterisation to ensure sensitive laboratory-based methodologies are utilised, thereby limiting the potential for false positives and environmental contamination.

In addition, researchers and public health authorities alike are urged to begin investigating the presence of MNPs in low socioeconomic areas, especially those identified as high risk due to exposure to contaminated water, food and living environments. Furthermore, the contamination of various clinical populations requires attention to understand variances in exposure and physiological consequences. In conjunction with laboratory-based analysis, complementary methodologies utilising surveys to characterise behaviour, alongside longitudinal studies within both animals and humans, are required to understand how various behaviours and exposures influence MNP contamination and its long-term effects on chronic disease and mortality. Clinical trials using behavioural interventions modifying MNP exposure, for example through dietary modifications, are urgently required to inform public health advice and international industry policy development. Additionally, research should seek to elucidate the potential impacts of specific environments (e.g. cities) and/or occupational hazards, especially in industries such as construction where individuals may be exposed to higher rates of MNPs associated with cardiovascular disease, such as poly vinyl chloride and polyethylene, as suggested by in vivo studies to date. An interdisciplinary approach which seeks to understand the multiple organ system interactions should be considered in order to advance our understanding of individual organ systems.

Limitations

Due to the rapidly evolving nature of this research field, this scoping review will require updating within the next 2 years. At this time, further research that may allow for a systematic review and meta-analysis to be conducted on the presence of MNPs in various tissues is currently precluded by a lack of available data and consistency within methodologies and reporting. Additionally, a lack of research investigating the presence and effect of MNPs on the lymphatic system prohibits a robust discussion on how this complementary organ system affects cardiovascular function. Methodological limitations were noted within some articles which may have affected reported results. For example, reports of haemolytic activity may be overestimated considering Djapovic et al. [32] washed RBCs with hypertonic (0.99%) NaCl. Similarly, Gopinath et al. [86] isolated RBCs by centrifugation without a density gradient medium, which may have led to some leucocytes remaining with the RBC concentration, resulting in the release of haemolytic enzymes. Marfella et al. [41] highlighted the potential for laboratory contamination during MNP detection in atherosclerotic plaques, despite rigorous efforts to minimise this risk. They also noted that while pyrolysis-gas chromatography-mass spectrometry provides sensitive detection of MNPs, it does not differentiate between MPs and NPs, limiting precise characterisation of particle size and type.

Conclusion

This systematic scoping review highlights the notable increase in research interest in this field since 2019, with all currently published studies reporting adverse effects on the cardiovascular system. Throughout their lives, humans are exposed to a multitude of MNPs with varying functionality, surface characteristics, chemical compositions and sizes every day. To date, research has identified the presence of MNPs within venous blood samples, cardiac tissue, thrombi, saphenous veins and atherosclerotic plaques, with implications for the prognosis of patients with cardiovascular disease and all-cause mortality. These findings, in conjunction with in vitro experimental designs, raise significant concern for the potential contribution of MNPs to cardiovascular pathologies such as atherosclerosis, cardiomyopathies, electrical abnormalities, congenital cardiovascular defects and infective pathologies. Multiple health authorities, including the WHO and the American College of Physicians, continue to call for urgent research in this field to elucidate the presence and effect of MNP bioaccumulation in humans, as well as to explore potential solutions [5, 87, 88]. Without further research, policy makers will be unable to act appropriately, and clinicians will lack the necessary guidance on how to assess, manage and educate their patients and the general public.