Related Experiment Video
Updated: Jan 10, 2026
Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
Microplastic exposure elicits sex-specific atherosclerosis development in lean low-density lipoprotein
Ting-An Lin1, Jianfei Pan2, Mya Nguyen2
1Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA, USA; Environmental Toxicology Graduate Program, University of California, Riverside, CA, USA.
Abstract:
Microplastics (MPs) are small plastic particles emerging as significant environmental pollutants and humans are ubiquitously exposed to MPs. MPs can be detected in human atherosclerotic plaques and are associated with a higher risk of cardiovascular disease (CVD) and stroke in humans. However, the impact of MP exposure on the cardiovascular system remains elusive. In the current study, we investigated the effects of exposure to MPs at an environmentally relevant dose on atherosclerosis development in male and female low-density lipoprotein receptor-deficient (LDLR-/-) mice. LDLR-/- mice were fed a semisynthetic low-fat (4.3 %), low-cholesterol (0.02 %) diet and exposed to 10 mg/kg body weight MPs via daily oral gavage for 9 weeks. Male and female LDLR-/- mice fed the low-fat diet did not develop obesity phenotype and exposure to MPs did not affect adiposity and circulating lipid profiles in those lean mice. Intriguingly, MP exposure increased atherosclerotic lesion areas in the aortic root by 63 % (p = 0.0185) and brachiocephalic artery by 624 % (p = 0.0541) in male LDLR-/- mice but did not significantly affect atherosclerosis in female mice. Single-cell RNA sequencing analysis of the whole aorta revealed that exposure to MPs affected the proportions and cellular processes of key atherogenesis-related cell types, especially endothelia cells. Consistently, MP exposure induced pro-atherogenic gene expression in murine primary endothelia cells and human endothelial cells in vitro. Our findings reveal the sex-specific atherogenic effects of MPs in vivo and provide mechanistic insights and new understanding of the impact of MPs on atherosclerosis development and CVD risk in humans.
Insights
Microplastic (MP) exposure significantly worsened atherosclerosis in male mice but not females, highlighting sex-specific cardiovascular risks. This research sheds light on how MPs impact cardiovascular disease development.
Area of Science:
- Environmental Health
- Cardiovascular Science
- Toxicology
Background:
- Microplastics (MPs) are pervasive environmental pollutants with ubiquitous human exposure.
- MPs have been found in human atherosclerotic plaques, suggesting a link to cardiovascular disease (CVD).
- The precise impact of MP exposure on the cardiovascular system remains largely unknown.
Purpose of the Study:
- To investigate the effects of environmentally relevant MP doses on atherosclerosis development.
- To examine potential sex-specific differences in MP-induced cardiovascular effects.
- To elucidate the cellular and molecular mechanisms underlying MP atherogenesis.
Main Methods:
- Low-density lipoprotein receptor-deficient (LDLR-/-) mice (male and female) were fed a low-fat diet and exposed to MPs (10 mg/kg/day) orally for 9 weeks.
- Atherosclerotic lesion areas in the aorta and brachiocephalic artery were quantified.
- Single-cell RNA sequencing (scRNA-seq) of aortic tissue and in vitro endothelial cell studies were performed.
Main Results:
- MP exposure did not alter adiposity or lipid profiles in lean LDLR-/- mice.
- A significant increase in atherosclerotic lesion areas was observed in male mice (aortic root: +63%, brachiocephalic artery: +624%).
- MP exposure did not significantly affect atherosclerosis in female mice, but altered endothelial cell populations and induced pro-atherogenic gene expression in vitro.
Conclusions:
- MP exposure exhibits sex-specific atherogenic effects in vivo.
- MPs can impact endothelial cell function and promote atherosclerosis, particularly in males.
- These findings provide mechanistic insights into MP-associated CVD risk and highlight the need for further investigation into sex differences.
