摘要
大量临床和基础研究证实雌激素具有显著的心血管保护效应,且该效应至少部分是通过增加血管内皮型一氧化氮合酶(eNOS)的表达和活性进而释放NO产生的。雌激素既可通过基因效应调节eNOS的表达,也可通过位于内皮细胞质膜微囊(caveolae)的ERα的一个亚群介导的非基因效应调节eNOS的活性。非基因效应与MAPK,PI3K/Akt等信号通路及内皮细胞质膜微囊密切相关,雌激素也可直接通过调节微囊蛋白-1表达而对eNOS的激活起负性调节作用。
Clinical and basic researches have demonstrated that estrogen has a multitude of biological effects on cardiovascular system. Further work has indicated that this is at least partially related to its capacity to stimulate nitric oxide （NO） production by endothelial NO synthase（eNOS）. The effects on eNOS abundane are primarily mediated at the level of gene transcription. Estrogen also has potent nongenomic effects on eNOS activity mediated by a subpopulation of ERot localized to caveolae in endothelial cells. Estrogen binding to ERot in caveolae leads to Goti activation, which mediates downstream events. The downstream signaling includes activation of tyrosine kinase-mitogen-activated protein kinase （MAPK） and phosphatidylinositol-3-kinase-Akt kinase （PI3K-Akt） , stimulation of heat shock protein 90 binding to eNOS, and perturbation of the local calcium environment, leading to eNOS phosphorylation and calmodulin-mediated eNOS stimulation. Recently, many investigations on caveolae provide an important clue for understanding signal transduction in plasma membrane, which might contribute to the effects of estrogen on cardiovascular system.
出处
《国际病理科学与临床杂志》
CAS
2007年第1期89-92,共4页
Journal of International Pathology and Clinical Medicine
基金
国家自然科学基金(30250010)~~
