Co-exposure of PM_2.5 and high-fat diet induce lipid metabolism reprogramming and vascular remodeling

Fine particulate matter (PM_2.5) 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 PM_2.5-induced cardiovascular disease. The purpose of this study was to investigate the impairment of lipid metabolism and vascular function by PM_2.5 and HFD exposure in ApoE^-/- mice. Oil red O staining indicated that co-treatment of PM_2.5 and HFD resulted in markedly lipid deposition in the mice aorta. Blood biochemical analysis demonstrated that co-exposure of PM_2.5 and HFD could cause dyslipidemia in vivo. Vascular Doppler ultrasound and histopathological analysis found that the functional and structural alterations with fibrosis and calcified remodeling of the vessels were detected after PM_2.5 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 PM_2.5 exposure; while Lipid and atherosclerosis signaling pathways had a critical role in PM_2.5-induced vascular injury. Results from validation experiments manifested that the release of supernatant in PM_2.5- 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-1β in aortic arch of mice were observed after co-exposure with PM_2.5 and HFD. Our data hinted that PM_2.5 could affect the lipid metabolism reprogramming and induce vascular remodeling, accompanied with synergistic effects of HFD.