Abstract 547: 7-Ketocholesterol-Mediated Alterations in Vascular Function: A Link Between Vascular and Metabolic Complications of Chronic Particulate Matter Exposure

BACKGROUND: Both human and animal studies have suggested a compelling link between inhaled particulate matter <2.5nm (PM2.5) exposure and acceleration of atherosclerosis. In this study, we assessed the hypothesis that 7-Ketocholesterol (7KC), a major redox product of cholesterol may mediate adverse vascular and metabolic effects of PM2.5 exposure. METHODS: Apolipoprotein E-/- (apoE-/-) mice were exposed to concentrated ambient PM2.5 or filtered air (FA) for 6 hours per day, 5 days per week for a total of 6 months in a versatile aerosol concentrator exposure system. Vasomotor tone changes were assessed in and atherosclerosis lesion quantification performed. 7KC and total cholesterol levels were determined by LC-MS in various tissues including aorta and 7KC accumulation and reverse transport studies in cultured murine macrophages subjected to PM2.5 exposure. eNOS activation and NO generation in response to 7KC exposure was assessed in cultured endothelial cells. RESULTS: PM2.5 increased aortic plaque (1.4-f...