Farhat M Y, Lavigne M C, Ramwell P W
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, D.C. 20007, USA.
FASEB J. 1996 Apr;10(5):615-24.
There is now strong epidemiological evidence that estrogen replacement therapy has a protective effect in postmenopausal women. The cardiovascular protective action of estrogen is reported to be mediated indirectly by an effect on lipoprotein metabolism and by a direct effect on the vessel wall itself. Estrogen is active both in vascular smooth muscle and endothelium. Functionally competent estrogen receptors have been identified in vascular smooth muscle cells, and specific binding sites have been demonstrated in endothelium. Estrogen administration promotes vasodilation both in human and experimental animals, in part by stimulating] prostacyclin and nitric oxide synthesis. Both the prostaglandin synthase and the constitutive nitric oxide synthase were recently reported to be induced by estrogen treatment. In vitro, estrogen exerts a direct inhibitory effect on the smooth muscle by inhibiting calcium influx. In addition, estrogen inhibits vascular smooth muscle cell proliferation. In vivo, estradiol-17 beta prevents neointimal thickening after balloon injury and in rabbit cardiac transplant allografts. These data are consistent with in vitro studies wherein estrogen inhibits [3H]thymidine uptake by arterial segments from porcine coronary artery as well as proliferation of rabbit aortic vascular smooth muscle cells induced by hyperlipedemic serum. Recent studies have also reported an effect of estrogen on directed vascular smooth muscle cell migration. Furthermore, like other steroids, the effect of estrogen on the vessel wall has a rapid nongenomic component involving membrane phenomena, such as alteration of membrane ionic permeability and activation of membrane-bound enzymes, as well as the classical genomic effect involving estrogen receptor activation and gene expression. The nature of these estrogen response genes in the vessel wall and their relation to vasodilation and antiproliferation remain to be determined.
目前有强有力的流行病学证据表明，雌激素替代疗法对绝经后女性具有保护作用。据报道，雌激素的心血管保护作用是通过对脂蛋白代谢的影响以及对血管壁本身的直接作用间接介导的。雌激素在血管平滑肌和内皮中均有活性。在血管平滑肌细胞中已鉴定出功能正常的雌激素受体，在内皮中也已证实有特异性结合位点。给予雌激素可促进人和实验动物的血管舒张，部分是通过刺激前列环素和一氧化氮的合成。最近有报道称，雌激素处理可诱导前列腺素合酶和组成型一氧化氮合酶。在体外，雌激素通过抑制钙内流对平滑肌产生直接抑制作用。此外，雌激素抑制血管平滑肌细胞增殖。在体内，雌二醇-17β可防止球囊损伤后和兔心脏移植同种异体移植物中的内膜增厚。这些数据与体外研究一致，在体外研究中，雌激素抑制猪冠状动脉动脉段的[3H]胸苷摄取以及高脂血症血清诱导的兔主动脉血管平滑肌细胞增殖。最近的研究还报道了雌激素对定向血管平滑肌细胞迁移的影响。此外，与其他类固醇一样，雌激素对血管壁的作用具有快速的非基因组成分，涉及膜现象，如膜离子通透性的改变和膜结合酶的激活，以及涉及雌激素受体激活和基因表达的经典基因组效应。血管壁中这些雌激素反应基因的性质及其与血管舒张和抗增殖的关系仍有待确定。
