Abstract Or114: Microplastic exposure elicits sex-specific atherosclerosis development in low-density lipoprotein receptor-deficient mice.

Introduction: Microplastics are small plastic particles emerging as significant environmental pollutants and humans are ubiquitously exposed to microplastics. Microplastics can also be detected in human atherosclerotic plaques and are associated with a higher risk of cardiovascular disease and stroke in humans. However, the impact of microplastic on the cardiovascular system remains elusive. This study aims to investigate the effects of microplastics exposure on atherosclerosis in a suitable animal model. Hypothesis: Exposure to microplastics affects atherosclerosis development in low-density lipoprotein LDL receptor-deficient (LDLR -/- ) mice. Methods: To investigate the effects of microplastic exposures on atherosclerosis development in vivo, male and female LDLR -/- mice were fed a low-fat AIN76 diet and exposed to 10 mg/kg body weight of microplastics via daily oral gavage for 9 weeks. Circulating lipid profiles and atherosclerotic plaques were analyzed and single-cell RNA sequencing (scRNA-seq) experiments were performed using the whole aorta. Results and Conclusions: Exposure to microplastics did not affect body weight and serum cholesterol and triglyceride levels in both male and female LDLR -/- mice. Intriguingly, microplastic exposure led to significantly increased atherosclerotic lesion sizes at the aortic roots of male but not female LDLR -/- mice. The scRNA-seq analysis of the whole aorta revealed that exposure to microplastic affected the proportions and cellular processes of key cell types involved in atherosclerosis development including endothelia cells and smooth muscle cells. QPCR analyses demonstrated that microplastic expose led to elevated pro-atherogenic gene expression in the intima of male LDLR -/- mice. Further, microplastic treatment induced endothelial cell dysfunction in human endothelial cells, leading to increased macrophage recruitment in vitro. These findings reveal the atherogenic effects of microplastics in vivo and the microplastic-induced endothelial cell dysfunction in vitro which may contribute to the increased atherosclerosis in exposed mice.