Sex differences in the formation of atherosclerosis lesion in apoE^-/-mice and the effect of 17β-estrodiol on protein S-nitrosylation

Abstract

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.