Real-world PM_2.5 exposure induces prostaglandin disruption and low-density lipoprotein oxidation, exacerbating atherogenesis in ApoE^−/− mice

Worsened air pollution has been linked to elevated rates of cardiovascular disease (CVD) morbidity and mortality. Atherosclerosis, a shared pathophysiological foundation for various CVD manifestations, plays a crucial role. Although foam cell formation is hypothesized to be a contributing factor, the precise mechanisms by which air pollution accelerates the advancement of atherosclerotic plaques remain unidentified. In this study, an atherosclerosis-susceptible apolipoprotein E-deficient (ApoE−/−) mouse model was employed to examine the influence of real-world environmental PM2.5 exposure on atherosclerosis. Metabolomic analysis was performed to identify potential biomarkers that may play a role in atherogenesis following PM2.5 exposure. Our findings revealed that mice fed a high-cholesterol diet (HCD) exhibited susceptibility to PM2.5 exposure, as evidenced by increased inflammation, enhanced fibrosis, and enlarged foam cell formation in the aorta. The interactive effects between PM2.5 exposure and HCD disrupted the secretion of certain chemokines. The metabolomic data provided additional insights into how PM2.5 exposure alters prostaglandin levels, contributing to the progression of atherosclerotic lesions. These findings enhance our understanding of the pivotal role of arachidonic acid metabolism in the etiology of PM2.5-induced cardiovascular risks and elucidate the mechanisms by which PM2.5 exposure leads to vascular damage in populations with high cholesterol intake.