Cyanidin-3-O-β-glucoside induces oxysterol efflux from endothelial cells: Role of liver X receptor alpha

ObjectivesOxidized 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 resultsThe 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.ConclusionsThese data uncover a novel mechanism by which C3G ameliorates oxysterol-induced oxidative damage on endothelial cells.

► C3G treatment prevents 7-KC-induced endothelial cells malfunction and apoptosis by upregulating ABCG1-dependent oxysterol efflux via LXRα. Our findings shed a new light on the therapeutic application of anthocyanin in the prevention of atherosclerosis. ► C3G increases ABCG1-mediated 7-KC efflux from HAECs. ► C3G decreases 7-KC-induced oxidative stress and apoptosis. ► C3G preserves eNos activity and NO bioavailability. ► The induction of ABCG1-mediated 7-KC efflux by C3G is LXRα dependent.