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.
Atherosclerosis. 2012 Aug;223(2):299-305. doi: 10.1016/j.atherosclerosis.2012.06.004. Epub 2012 Jun 16.
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.
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.
These data uncover a novel mechanism by which C3G ameliorates oxysterol-induced oxidative damage on endothelial cells.
氧化固醇对内皮细胞有毒性，在促进动脉粥样硬化形成中起核心作用。在这项研究中，我们评估了花色苷（一类类黄酮化合物）对内皮细胞中氧化固醇外排的影响及其潜在机制。
用花色苷矢车菊素-3-O-β-葡萄糖苷（C3G）孵育人主动脉内皮细胞（HAECs）不同时间。C3G 以剂量依赖的方式上调 HAECs 中 ABCG1 和 ABCA1 的表达。此外，C3G 以 ABCG1 依赖的方式促进胆固醇主要是 7-酮胆固醇（7-KC）从 HAECs 中的流出。结果，C3G 减轻了 7-KC 介导的 HAECs 中活性氧（ROS）和细胞凋亡的增加。此外，C3G 处理逆转了 7-KC 对内皮型一氧化氮合酶（eNOS）活性的抑制，从而维持了一氧化氮（NO）的生物利用度。C3G 通过激活肝 X 受体α（LXRα）诱导 HAECs 中 ABCG1 的表达及其介导的 7-KC 外排，这通过药理学或 LXRα 的小干扰 RNA 抑制后 ABCG1 表达的阻断得到证实。
这些数据揭示了 C3G 改善氧化固醇引起的内皮细胞氧化损伤的新机制。
