Microplastics Make Male Arteries Vulnerable While Females Are Spared

Tiny plastic fragments in our food and water may be quietly hardening male arteries long before a heart attack ever strikes. In new research from the University of California, Riverside, scientists report that everyday level microplastic exposure sharply worsened artery clogging in male mice while leaving females largely untouched, raising urgent questions about how plastic pollution collides with cardiovascular risk.

The study, an experimental mouse study led by biomedical scientist Changcheng Zhou at the University of California, Riverside and published November 17, 2025 in Environment International, exposed male and female low density lipoprotein receptor deficient mice to 10 milligrams per kilogram of polystyrene microplastics by mouth each day for nine weeks while the animals ate a lean, low fat, low cholesterol diet. In males, this environmentally relevant exposure increased plaque area by 63 percent in the aortic root and by roughly six fold in the brachiocephalic artery, while females on the same regimen showed no significant change in plaque formation.

Microplastics are no longer just a problem in oceans and soil. They now turn up in drinking water, food, indoor air and, increasingly, inside human tissues, including atherosclerotic plaques taken from patients. That background raised a disturbing possibility for Zhou and colleagues. If plastic particles can reach human arteries, are they simply markers of exposure, or active players in the slow buildup of fatty, inflamed plaque that drives heart attacks and strokes

To get a clearer answer, the team chose a classic heart disease model, mice lacking the LDL receptor, which are prone to atherosclerosis. Unlike many earlier studies that layered multiple risk factors, the researchers worked hard to strip away confounders. Both male and female mice were kept lean on a semisynthetic diet with just 4.3 percent fat and 0.02 percent cholesterol, a regimen known to produce plaques without obesity or diabetes. Microplastics did not change body weight, fat mass, or blood lipid levels in either sex.

That clean metabolic profile is part of what makes the results so striking. Despite normal cholesterol and triglycerides, male mice given microplastics developed markedly larger plaques in two key arterial sites. The aortic root, the section of the aorta attached directly to the heart, showed a 63 percent increase in lesion area. The brachiocephalic artery, a branch vessel in the upper chest that is particularly prone to dangerous lesions, showed an even more dramatic enlargement of plaque.

A Plastic World Inside The Arteries

The team then asked a simple but critical question. Were the plastic particles actually reaching the diseased parts of the arteries, or only circulating past them They repeated the experiment with red fluorescent polystyrene particles and examined the mice under the microscope. The labeled microplastics appeared inside the plaques of male animals and along the intimal layer, the thin sheet of endothelial cells that lines the vessel wall, mirroring recent human reports of plastic fragments in arterial lesions.

Those endothelial cells became the focus of the next phase of the work. Using single cell RNA sequencing, a technique that profiles the gene activity of thousands of individual cells at once, the researchers built a transcriptomic atlas of the aorta in control and microplastic exposed male mice. They identified 17 major cell clusters and found that microplastic exposure reshaped several of them, increasing the proportions of endothelial cells, stressed smooth muscle cells, smooth muscle derived macrophages and even oligodendrocyte like cells, while reducing B cells and T cells.

Within the endothelial compartment, the damage was even clearer. The team resolved three distinct endothelial subclusters, including a population of macrophage like endothelial cells that expressed high levels of Cd36 and Fabp4, genes linked to lipid uptake and inflammatory signaling. Microplastic exposure shifted the balance toward this pro atherogenic subcluster and pushed endothelial cells along a trajectory marked by rising expression of Cd36, Fabp4 and other plaque promoting genes.

“We found endothelial cells were the most affected by microplastic exposure,” Zhou said. “Since endothelial cells are the first to encounter circulating microplastics, their dysfunction can initiate inflammation and plaque formation.”

Laboratory experiments outside the animal confirmed that picture. When the team exposed primary endothelial cells from mice and human HMEC 1 endothelial cells to microplastics, the cells switched on a suite of inflammatory and atherogenic genes, including Cd36, Fabp4, Il 1α, Il 6, Nlrp3 and Ikkβ. In the human cells, microplastics also boosted reactive oxygen species, a marker of oxidative stress that is closely tied to vascular injury.

Why Male Arteries Took The Hit

The most unsettling aspect of the work is not simply that microplastics can worsen atherosclerosis, but that they did so only in male mice under these conditions. Female LDL receptor deficient mice on the same low fat diet and plastic exposure remained lean, had normal lipid levels and did not show significant increases in plaque area at either arterial site. That sex specific vulnerability fits with a larger cardiovascular literature in which males and females often show different trajectories of risk.

“Our study provides some of the strongest evidence so far that microplastics may directly contribute to cardiovascular disease, not just correlate with it,” Zhou said. “The surprising sex-specific effect, harming males but not females, could help researchers uncover protective factors or mechanisms that differ between men and women.”

Those protective factors are not yet known. The press release notes that sex chromosomes and sex hormones, particularly the well documented protective effects of estrogen on atherosclerosis, are likely suspects. It is possible that female hormones buffer the endothelial stress triggered by microplastics, or that male and female vascular cells handle particles differently at a molecular level. The current study was not designed to untangle those mechanisms, but it points directly toward the need for that work.

The authors are also careful about the limits of their model. They used a single microplastic dose and a nine week exposure window, in lean mice that develop relatively early lesions. That means they cannot yet say how different doses, particle sizes or exposure durations might influence plaque complexity or vulnerability, nor how microplastics interact with other common risk factors such as high fat diets, obesity or diabetes. Future experiments will need to explore a broader range of conditions and, ultimately, human populations.

Even so, the findings carry practical implications in a world where microplastic pollution is steadily rising and where cardiovascular disease remains the leading global killer. Recent human studies have already linked higher microplastic burdens in arterial plaques and blood to worse cardiovascular outcomes. This new mouse work shows a plausible biological route from ingested plastic particles to disturbed endothelial biology and accelerated plaque growth, at least in males.

Zhou stresses that individuals cannot fully opt out of exposure, but small choices still matter.

“It is nearly impossible to avoid microplastics completely,” Zhou said in the press release, noting that they are now embedded in food, water and air. He points instead to strategies that reduce contact where possible, such as limiting plastic food and water containers, cutting back on single use plastics and favoring less processed foods, alongside the familiar pillars of cardiovascular health, including diet, physical activity and risk factor management.

On the research side, the team plans to probe how different types and sizes of microplastics affect vascular cells, and to dissect the molecular pathways that govern endothelial dysfunction in male and female arteries. As plastic particles continue to permeate ecosystems and bodies, their work suggests that preventing heart disease in the twenty first century may require thinking not only about cholesterol and blood pressure, but also about the invisible debris in our environment.

Environment International: 10.1016/j.envint.2025.109938