Preliminary Research Of Senp1's Functions In The Pathogenesis Of Atherosclerosis

Atherosclerosis and its related atherothrombotic vascular disease is the leading cause of death worldwide. Chronic nonresolving inflammation and dysregulation of lipid metabolism make great contributions to the pathogenesis of atherosclerosis. The macrophages play an important role in the process by involving in both inflammation and lipid metabolism. Our previous study shows that SENP1(sentrin/SUMO-specific protease 1) deficiency can downregulate the activation of macrophages. Thus our hypothesis is that SENP1 involve in the pathogenesis of atherosclerosis through regulating macrophages'function. In this study, we generate SENP1+/+;Apoe-/- and SENP1+/-;Apoe-/- mice by crossing SENP1+/- with Apoe-/- mice, a genetic mouse model predisposed to diet-induced atherosclerosis. After feeding with western diet for 12 weeks, by en face analysis and aortic root section staining we find that SENP1+/-;Apoe-/- mice have tendency to develop more severe atherosclerosis lesions. Meanwhile, in SENP1+/- peritoneal macrophages and SENP1 silencing macrophage cell line RAW264.7, we observe that down-expression of SENP1 could upregulate the expression of FABP4, an important molecular that modulate both inflammation and lipid trafficking in macrophage, and accelerate the formation of foam cells. These data reveal that SENP1 may play a potential protective role in the pathogenesis of atherosclerosis.