Yun Wang1, Yuhua Zhang, Xiaoming Wang, Yan Liu, Min Xia. 1. Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province 510080, PR China.
Abstract
OBJECTIVES: Oxidized sterols are toxic to endothelial cells and play a central role in promoting atherogenesis. In this study, we evaluated the impact of anthocyanin, a class of flavonoid compounds, on oxysterol efflux from endothelial cells and the underlying mechanism. METHODS AND RESULTS: The human aortic ECs (HAECs) were incubated with anthocyanin cyanidin-3-O-β-glucoside (C3G) for different times. C3G treatment upregulates ABCG1 and ABCA1 expression in a dose-dependent manner in HAECs. Moreover, C3G promotes the efflux of cholesterol mainly 7-ketocholesterol (7-KC) from HAECs in an ABCG1-dependent manner. As a result, C3G abrogated the 7-KC-mediated increase of reactive oxygen species (ROS) and apoptosis in HAECs. Furthermore, C3G treatment reverses the inhibition of endothelial nitric oxide synthase (eNOS) activity by 7-KC, leading to the preservation of nitric oxide (NO) bioavailability. The induction of ABCG1 and its mediated 7-KC efflux from HAECs by C3G resulted from liver X receptor α (LXRα) activation, which was confirmed by its blockage of ABCG1 expression after pharmacological or small interfering RNA inhibition of LXRα. CONCLUSIONS: These data uncover a novel mechanism by which C3G ameliorates oxysterol-induced oxidative damage on endothelial cells.
OBJECTIVES: Oxidized sterols are toxic to endothelial cells and play a central role in promoting atherogenesis. In this study, we evaluated the impact of anthocyanin, a class of flavonoid compounds, on oxysterol efflux from endothelial cells and the underlying mechanism. METHODS AND RESULTS: The human aortic ECs (HAECs) were incubated with anthocyanin cyanidin-3-O-β-glucoside (C3G) for different times. C3G treatment upregulates ABCG1 and ABCA1 expression in a dose-dependent manner in HAECs. Moreover, C3G promotes the efflux of cholesterol mainly 7-ketocholesterol (7-KC) from HAECs in an ABCG1-dependent manner. As a result, C3G abrogated the 7-KC-mediated increase of reactive oxygen species (ROS) and apoptosis in HAECs. Furthermore, C3G treatment reverses the inhibition of endothelial nitric oxide synthase (eNOS) activity by 7-KC, leading to the preservation of nitric oxide (NO) bioavailability. The induction of ABCG1 and its mediated 7-KC efflux from HAECs by C3G resulted from liver X receptor α (LXRα) activation, which was confirmed by its blockage of ABCG1 expression after pharmacological or small interfering RNA inhibition of LXRα. CONCLUSIONS: These data uncover a novel mechanism by which C3G ameliorates oxysterol-induced oxidative damage on endothelial cells.