Murphy Elizabeth, Steenbergen Charles
Head Cardiac Physiology Section, Vascular Medicine Branch, National Heart, Lung, and Blood Institute/NIH, 10 Center Drive, Bethesda, MD 20892, USA.
Heart Fail Rev. 2007 Dec;12(3-4):293-300. doi: 10.1007/s10741-007-9035-0.
A number of epidemiological and animal studies have suggested a cardioprotective role for estrogen. This review will focus on the cardioprotective role of estrogen in ischemia-reperfusion injury. Estrogen binding to receptors can lead to altered gene expression and estrogen has been shown to induce expression of a number of genes that have been suggested to be important in cardioprotection. Estrogen is reported to increase expression of the plasma membrane glucose transporter GLUT4 and to increase carbohydrate metabolism. Estrogen has also been reported to increase mitochondrial biogenesis and to alter mitochondrial generation of reactive oxygen species. Estrogen results in upregulation of cardiac eNOS and nNOS, which have been shown previously to be important mediators of cardioprotection. Nitric oxide has been shown to result in S-nitrosylation and inhibition of the L-type calcium channel, thereby reducing calcium loading during ischemia. Nitric oxide has also been reported to inhibit complex I and inhibition of complex I has been reported to reduce activation of the mitochondrial permeability transition pore. Nitric oxide has been shown to result in activation of the mitochondrial K(ATP) channel, which has been shown to be involved in cardioprotection. Estrogen can also activate rapid non-genomic pathways that activate cardioprotective-signaling pathways such as the phosphatidylinositol-3-kinase (PI-3 kinase) pathway which has also been shown to initiate protection. Taken together, estrogen by genomic and non-genomic pathways can result in the initiation of a number of signaling pathways that enhance cardioprotection.
多项流行病学和动物研究表明雌激素具有心脏保护作用。本综述将聚焦于雌激素在缺血再灌注损伤中的心脏保护作用。雌激素与受体结合可导致基因表达改变，并且已表明雌激素可诱导许多被认为在心脏保护中起重要作用的基因表达。据报道，雌激素可增加质膜葡萄糖转运蛋白GLUT4的表达并增加碳水化合物代谢。据报道，雌激素还可增加线粒体生物合成并改变线粒体活性氧的生成。雌激素导致心脏内皮型一氧化氮合酶（eNOS）和神经元型一氧化氮合酶（nNOS）上调，此前已表明它们是心脏保护的重要介质。一氧化氮已被证明可导致L型钙通道的S-亚硝基化并抑制该通道，从而减少缺血期间的钙负荷。据报道，一氧化氮还可抑制复合体I，并且据报道抑制复合体I可减少线粒体通透性转换孔的激活。一氧化氮已被证明可导致线粒体ATP敏感性钾通道（K(ATP)通道）激活，该通道已被证明与心脏保护有关。雌激素还可激活快速非基因组途径，这些途径可激活心脏保护信号通路，如磷脂酰肌醇-3-激酶（PI-3激酶）途径，该途径也已被证明可启动保护作用。综上所述，雌激素通过基因组和非基因组途径可引发多种增强心脏保护的信号通路。
