Cardioprotective effect of estrogen and raloxifene

雌激素和雷洛昔芬的心脏保护作用

• 批准号: 14571560
• 负责人: OHMICHI Masahide
• 金额: $ 2.18万
• 依托单位: Osaka University (2004)Yamagata University (2002-2003)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571560/
• 关键词: estrogen; raloxifene; vasodilatation; atherosclerosis; Akt; apoptosis; survival factor; ERα; 血管内皮機能; 両側卵巣摘出術; HUVEC; Survival factor; アポトーシス; 血管内皮細胞; Akt

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.

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。雌激素对血管有多种直接影响，例如雌激素诱导的血管舒张增加和抑制血管对损伤的反应以及动脉粥样硬化的发展。尽管雌激素和雷尔昔芬都激活了血液中抑制血管损伤的机制，而血管抑制了血管造成的损伤的机制，并抑制了血管造成的损伤和累积的机制。我们确定雌激素和雷昔芬都降低了凋亡并起到生存因子的作用。由于通过基因转染将Akt-Bad级联阻塞和抑制剂的添加减轻了雌激素和雷昔芬的凋亡减少，因此Akt-Bad级联反应参与雌激素和raloxifene对血管对损伤的反应的抑制。此外，我们确定雌激素和雷昔芬是一种彻底的ERα的生存因子，但最后没有ERα，我们检查了手术更年期对臂动脉流介导的扩张的血管内皮功能的作用。手术更年期1周后，血管内皮的功能显着改善。

项目成果

Cardiovascular effects of SERM

SERM 对心血管的影响

• 发表时间: 2004
• 期刊: Clin Calcium 14
• 作者: Ohmichi M.;et al.
• 通讯作者: et al.