Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Department of Public Health&College of Clinical Medicine, Xi'an Medical University, Xi'an, Shaanxi 710021, China.
Key Laboratory for Space Biosciences & Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China.
Biomed Pharmacother. 2018 Mar;99:1014-1021. doi: 10.1016/j.biopha.2018.01.145. Epub 2018 Feb 20.
Estrogen plays aprotective effect on the cardiovascular system. Abnormal vascular smooth muscle cells (VSMCs) are involvedin the progress of atherosclerosis. However, the effect of estrogen on VSMCs is still unclear. The purpose of this study is to investigate the effect of 17β-estradiol (E2), a potent endogeneous estrogen, on the development of atherosclerosis and its potential mechanisms. In vivo, the formation of atherosclerotic lesions and the extent of protein S-nitrosylation were compared between female and male apoE mice to assess the effect of estrogen. It showedthat the gross lesion area of the aorta tree, the lesion area atthe aortic root and the contents of lipids, macrophages and VSMCs were significantly less in female apoE mice than those in male mice (p < 0.05). In addition, compared with male mice, plasma NO level and protein S-nitrosylation level of VSMCs were significantly higher in female mice (p < 0.01). Rat VSMCs (rVSMCs) were successfully isolated. In vitro, the levels of NO and protein S-nitrosylation in rVSMCs with E2 treatment were also assessed. The result revealed that E2 treatment reversed the ox-LDL-induced superoxide anion level increaseand the ox-LDL-induced NO and protein S-nitrosylation levels decrease in rVSMCs. Our data indicated that female is less susceptible to atherosclerosis.It might be becauseestrogenpromotes NO production and down-regulatessuperoxide anion level, which further upregulates the protein S-nitrosylation level of VSMCs against the occurrence and development of atherosclerosis.
雌激素对心血管系统具有保护作用。异常的血管平滑肌细胞（VSMCs）参与动脉粥样硬化的进展。然而，雌激素对 VSMCs 的作用尚不清楚。本研究旨在探讨 17β-雌二醇（E2），一种有效的内源性雌激素，对动脉粥样硬化发展的影响及其潜在机制。在体内，比较了雌性和雄性 apoE 小鼠的动脉粥样硬化病变形成和蛋白质 S-亚硝基化程度，以评估雌激素的作用。结果表明，雌性 apoE 小鼠主动脉树的大体病变面积、主动脉根部的病变面积以及脂质、巨噬细胞和 VSMCs 的含量明显低于雄性小鼠（p<0.05）。此外，与雄性小鼠相比，雌性小鼠的血浆 NO 水平和 VSMCs 的蛋白质 S-亚硝基化水平明显更高（p<0.01）。成功分离了大鼠 VSMCs（rVSMCs）。在体外，还评估了 E2 处理后 rVSMCs 中 NO 和蛋白质 S-亚硝基化的水平。结果表明，E2 处理逆转了 ox-LDL 诱导的超氧阴离子水平升高以及 ox-LDL 诱导的 rVSMCs 中 NO 和蛋白质 S-亚硝基化水平降低。我们的数据表明，女性对动脉粥样硬化的易感性较低。这可能是因为雌激素促进了 NO 的产生，并下调了超氧阴离子水平，进而上调了 VSMCs 的蛋白质 S-亚硝基化水平，从而抑制了动脉粥样硬化的发生和发展。
