Rubanyi Gabor M, Johns Anthony, Kauser Katalin
Department of Gene Therapy, Berlex Biosciences, Richmond, CA, USA.
Vascul Pharmacol. 2002 Feb;38(2):89-98. doi: 10.1016/s0306-3623(02)00131-3.
Animal studies evaluating gender difference, the effects of gonadectomy and estrogen replacement and clinical studies in post-menopausal women with and without estrogen replacement therapy (ERT) proved that estrogen exerts significant benefits on the cardiovascular system. Since effects on the plasma lipoprotein profile is responsible for only approximately 25-40% of the cardiovascular protection exerted by estrogens, it is postulated that direct effects of estrogen on the vascular wall must play an important role. Indeed, experimental and clinical evidence accumulated over the past decade, and reviewed briefly here, indicate that at least a part of cardiovascular benefits of 17 beta-estradiol can be attributed to the direct effect of the ovarian sex steroid hormone on vascular endothelial cells. Maintenance and upregulation of endothelial nitric oxide production and suppression of EDCF generation by 17 beta-estradiol may play an important role in preventing or reversing endothelial dysfunction, associated with atherosclerosis, hypertension and other cardiovascular diseases. Stimulation of angiogenesis (especially collateral vessel formation in ischemic tissues) by the ovarian steroid hormone could be beneficial in coronary artery disease, peripheral vascular disease, cerebral ischemia (stroke) and congestive heart failure. Despite these indisputable beneficial effects, several key questions remain to be answered in the future, including the better understanding of the apparently opposite effects of estrogen on prevention of cardiovascular disease vs. treatment of existing disease.
评估性别差异、性腺切除术和雌激素替代作用的动物研究,以及针对接受和未接受雌激素替代疗法(ERT)的绝经后女性开展的临床研究均证明,雌激素对心血管系统具有显著益处。由于雌激素对心血管系统的保护作用中,仅有约25%-40%是通过影响血浆脂蛋白水平实现的,因此推测雌激素对血管壁的直接作用必定发挥着重要作用。事实上,过去十年积累的实验和临床证据(在此简要回顾)表明,17β-雌二醇对心血管系统的益处至少有一部分可归因于这种卵巢性类固醇激素对血管内皮细胞的直接作用。17β-雌二醇维持并上调内皮一氧化氮生成,抑制内皮依赖性收缩因子生成,这在预防或逆转与动脉粥样硬化、高血压及其他心血管疾病相关的内皮功能障碍中可能发挥重要作用。卵巢类固醇激素对血管生成的刺激作用(尤其是缺血组织中侧支血管的形成)可能对冠状动脉疾病、外周血管疾病、脑缺血(中风)和充血性心力衰竭有益。尽管有这些无可争议的有益作用,但未来仍有几个关键问题有待解答,包括更好地理解雌激素在预防心血管疾病与治疗现有疾病方面明显相反的作用。