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It is reported that oxidative stress homeostasis was involved in PM 2.5 -induced foam cell formation and progression of atherosclerosis, but the exact molecular mechanism is still unclear. Melatonin is an effective antioxidant that could reverse the cardiopulmonary injury. The main purpose of this study is to investigate the latent mechanism of PM 2.5 -triggered atherosclerosis development and the protective role of melatonin administration. Vascular Doppler ultrasound showed that PM 2.5 exposure reduced aortic elasticity in ApoE -/- mice. Meanwhile, blood biochemical and pathological analysis demonstrated that PM 2.5 exposure caused dyslipidemia, elicited oxidative damage of aorta and was accompanied by an increase in atherosclerotic plaque area; while the melatonin administration could effectively alleviate PM 2.5 -induced macrophage M1 polarization and atherosclerosis in mice. Further investigation verified that NADPH oxidase 2 (NOX2) and mitochondria are two prominent sources of PM 2.5 -induced ROS production in vascular macrophages. Whereas, the combined use of two ROS-specific inhibitors and adopted with melatonin markedly rescued PM 2.5 -triggered macrophage M1 polarization and foam cell formation by inhibiting NOX2-mediated crosstalk of Keap1/Nrf2/NF-κB and TLR4/TRAF6/NF-κB signaling pathways. Our results demonstrated that NOX2-mediated oxidative stress homeostasis is critical for PM 2.5 -induced atherosclerosis and melatonin might be a potential treatment for air pollution-related cardiovascular diseases., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Ambient and indoor air pollution contributes annually to approximately seven million premature deaths. Air pollution is a complex mixture of gaseous and particulate materials. In particular, fine particulate matter (PM 2.5 ) plays a major mortality risk factor particularly on cardiovascular diseases through mechanisms of atherosclerosis, thrombosis and inflammation. A review on the PM 2.5 -induced atherosclerosis is needed to better understand the involved mechanisms. In this review, we summarized epidemiology and animal studies of PM 2.5 -induced atherosclerosis. Vascular endothelial injury is a critical early predictor of atherosclerosis. The evidence of mechanisms of PM 2.5 -induced atherosclerosis supports effects on vascular function. Thus, we summarized the main mechanisms of PM 2.5 -triggered vascular endothelial injury, which mainly involved three aspects, including vascular endothelial permeability, vasomotor function and vascular reparative capacity. Then we reviewed the relationship between PM 2.5 -induced endothelial injury and atherosclerosis. PM 2.5 -induced endothelial injury associated with inflammation, pro-coagulation and lipid deposition. Although the evidence of PM 2.5 -induced atherosclerosis is undergoing continual refinement, the mechanisms of PM 2.5 -triggered atherosclerosis are still limited, especially indoor PM 2.5 . Subsequent efforts of researchers are needed to improve the understanding of PM 2.5 and atherosclerosis. Preventing or avoiding PM 2.5 -induced endothelial damage may greatly reduce the occurrence and development of atherosclerosis.