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。雌激素对血管的直接作用有多种，如增强血管舒张功能，抑制血管对损伤的反应和动脉粥样硬化的发展，虽然雌激素和雷洛昔芬都能激活内皮细胞合成NO，但雌激素和雷洛昔芬抑制血管对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凋亡，并作为一种生存因子。由于通过基因转染和添加抑制剂阻断Akt-BAD级联反应减弱了雌激素和雷洛昔芬对细胞凋亡的减少，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。雌激素和雷洛昔芬通过ERα而不是ERα发挥生存因子的作用。最后，我们通过肱动脉血流介导的血管内皮舒张功能，检测了手术绝经对血管内皮功能的影响。手术绝经1周后血管内皮功能明显下降。

项目成果

Rapid changes of flow-mediated dilatation after surgical menopause.

手术绝经后血流介导的扩张迅速变化。

• 发表时间: 2003
• 期刊: Maturitas 44
• 作者: Ohmichi M

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.