Cardioprotective effect of estrogen and raloxifene

最近的证据表明，雌激素对血管的直接作用有助于雌激素的心脏保护作用。雌激素对血管的直接作用有多种，如雌激素引起的血管扩张增加、血管对损伤反应的抑制和动脉粥样硬化的形成等。虽然雌激素和雷洛昔芬都能促进内皮细胞中NO的合成，但其抑制血管损伤反应的机制尚不清楚。我们发现雌激素和雷洛昔芬都能减少细胞的凋亡，并作为一个生存因子。由于通过基因导入和添加抑制剂阻断Akt-Bad级联反应可以减弱雌激素和雷洛昔芬对细胞凋亡的抑制作用，因此Akt-Bad级联反应参与了雌激素和雷洛昔芬对血管损伤反应的抑制。此外，我们通过ERα证实雌激素和雷洛昔芬是一个生存因子，而不是ERα。最后，我们通过肱动脉血流介导的扩张来观察手术绝经对血管内皮功能的影响。手术绝经1周后，血管内皮细胞功能明显下降。

Recent evidence suggests that the direct actions of estrogen on blood vessels contribute to the cardioprotective effects of estrogen. There are many kinds of direct effects of estrogen on blood vessels, such as estrogen-induced increases of vasodilatation and inhibition of the response of blood vessels to injury and the development of atherosclerosis.Although both estrogen and raloxifene activate NO synthesis in endothelial cells, the mechanism of inhibition of the response of blood vessels to injury by estrogen and raloxifene remains unclear. We identified that both estrogen and raloxifene decrease the apoptosis and act as a survival factor. Since blockage of Akt-BAD cascade by gene transfection and addition of inhibitor attenuated the decrement of apoptosis by estrogen and raloxifene, Akt-BAD cascade is involved in the inhibition of the response of blood vessels to injury by estrogen and raloxifene. Moreover, we identified that estrogen and raloxifene act as a survival factor thorough ERα, but not ERα Lastly, we examined the effect of surgical menopause on the function of vascular endothelium by brachial artery flow mediated dilatation. The function of vascular endothelium was significantly decreased after 1 week of surgical menopause.