Mechanism of anti-atherosclerotic effect of estrogen

临床研究：动脉粥样硬化性心血管疾病（CVD）是绝经后妇女发病和死亡的主要原因。雌激素已被证明可以抑制动脉粥样硬化并帮助维持动脉功能。测量颈动脉内膜-中膜厚度（IMT）用于动脉粥样硬化过程的病理生理学研究，以寻找引发颈动脉粥样硬化早期发展的因素。HRT期间，ERT组患者的平均IMT和最大IMT均显著降低，而对照组患者的IMT变化无统计学意义。纵向分析显示脂质代谢指标和p选择显著降低。这些数据正在提交中（Nishio等人）。体外研究：在人脐静脉内皮细胞和sv40转化大鼠肺血管内皮细胞的研究中，17β-雌二醇（E2）引起eNOS的急性激活，而不是17α-E2，该激活不受放线菌素D的影响，并被纯雌激素受体拮抗剂ici - 182780特异性阻断。此外，17α-E2通过akt依赖性机制诱导eNOS激活，而该机制是由er α通过非基因组机制介导的（Hisamoto等人）。在血管平滑肌细胞中，E2抑制pdgf诱导的细胞增殖。但E2抗增殖作用的具体机制尚在研究中。

Clinical study:Atherosclerotic cardiovascular disease (CVD) is the major cause of morbidity and mortality in postmenopausal women. Estrogens have been shown to inhibit atherosclerosis and to help maintaining arterial function.Measurement of intima-media thickness (IMT) of the carotid artery is used in pathophysiological studies of the atherosclerotic process to search the factors initiating the early development of atherosclerosis in the carotid arteries.IMT in the ERT group patients showed a significant decrease during HRT period in both mean and maximum IMT, while the control group patients showed no statistically significant change. Lipid metabolism markers and P-selection showed significant decrease in the longitudinal analysis. These data are under submission (Nishio et al.).In vitro study:In studies of human umbilical vein endotherial cells and SV40-transformed rat lung vascular endotherial cells, 17β-estradiol (E2), but not 17α-E2, caused acute activation of eNOS that was unaffected by actinomycin D and was specifically blocked by the pure estrogen receptor antagonist ICI-182,780. Furthermore, 17α-E2 induced eNOS activation through an Akt-dependent mechanism, which is mediated by Erαvia a nongenomic mechanism (Hisamoto et al.).In vascular smooth muscle cells, E2 suppressed PDGF-induced cell proliferation. But, the detailed mechanism of anti-proliferative effect of E2 is under investigation.