Quercetin mitigates cardiovascular injury induced by subchronic exposure to PM2.5 and O3 via modulation of lipid metabolism and MAPK signaling

Fine particulate matter (PM_2.5) and ozone (O₃) are key air pollutants linked to a higher risk of cardiovascular diseases. However, the effects of combined PM_2.5 and O₃ exposure on cardiovascular health remain unclear. In this study, C57BL/6 J mice were exposed to PM_2.5 suspension (6 mg/kg body weight) and/or O₃ (1.00 ppm) for 8 weeks, resulting in abnormal myocardial enzyme profiles. Sirius Red and Masson's trichrome staining confirmed myocardial fibrosis and collagen deposition in the mice. Further experiments demonstrated that PM_2.5 and O₃ subchronic co-exposure increased cardiac inflammatory factors, phosphorylation of p38, ERK1/2, and JNK, as well as cardiomyocyte apoptosis. Subsequently, an atherosclerosis model was established using ApoE-/- mice, which were exposed to PM_2.5 suspension (6 mg/kg b.w.) and O₃ (1.00 ppm) for 8 consecutive weeks. During this period, the mice were treated with quercetin, a flavonoid antioxidant derived from plants. Our findings demonstrated that PM_2.5 and O₃ co-exposure promoted the progression of atherosclerosis. In contrast, administration of quercetin in PM_2.5- and O₃-exposed ApoE-/- mice significantly reduced cardiac enzyme markers, myocardial fibrosis, collagen deposition, cardiomyocyte apoptosis, and activation of the MAPK signaling pathway. Omics results revealed that quercetin primarily exerted its protective effects in atherosclerotic mice by modulating phosphatidylcholine, phosphatidylethanolamine, as well as the inflammatory signaling pathways. In summary, subchronic exposure to PM_2.5 and O₃ contributes to cardiac injury and accelerates the progression of atherosclerosis in mice and this detrimental effect can be mitigated by the administration of quercetin. Our study presents novel strategies aimed at mitigating the cardiovascular health impacts of air pollution.