Co-exposure of PM(2.5 )and high-fat diet induce lipid metabolism reprogramming and vascular remodeling

Fine particulate matter (PM2.5) exposure has been proved to increase the cardiovascular disease risk. However, there is a lack of comprehensive knowledge on whether a high-fat diet (HFD) affects PM2.5-induced cardiovas-cular disease. The purpose of this study was to investigate the impairment of lipid metabolism and vascular function by PM2.5 and HFD exposure in ApoE-/-mice. Oil red O staining indicated that co-treatment of PM2.5 and HFD resulted in markedly lipid deposition in the mice aorta. Blood biochemical analysis demonstrated that co-exposure of PM2.5 and HFD could cause dyslipidemia in vivo. Vascular Doppler ultrasound and histopatho-logical analysis found that the functional and structural alterations with fibrosis and calcified remodeling of the vessels were detected after PM2.5 and HFD exposure. For in-depth study, the genome-wide transcriptional analysis performed in macrophages was further revealed that the endoplasmic reticulum stress, immune system process, regulation of cell proliferation etc. were response to PM2.5 exposure; while Lipid and atherosclerosis signaling pathways had a critical role in PM2.5-induced vascular injury. Results from validation experiments manifested that the release of supernatant in PM2.5- or ox-LDL-treated macrophages could decrease the cell viability and increase the lipid ROS in vascular smooth muscle cells (VSMCs). Moreover, the up-regulations of CCL2, IL-6 and IL-1 beta in aortic arch of mice were observed after co-exposure with PM2.5 and HFD. Our data hinted that PM2.5 could affect the lipid metabolism reprogramming and induce vascular remodeling, accompanied with synergistic effects of HFD.