Booth Erin A, Lucchesi Benedict R
Department of Pharmacology, University of Michigan Medical School, 1301C Medical Science Research Building III, Ann Arbor, MI 48109-5632, USA.
Cardiovasc Toxicol. 2008 Fall;8(3):101-13. doi: 10.1007/s12012-008-9022-2. Epub 2008 Aug 6.
Before menopause, a woman has a relatively low risk for developing cardiovascular disease. After menopause, however, the risk increases nearly twofold and cardiovascular disease remains the number one cause of death among women. Observational trials and studies in animal models of cardiovascular disease suggested that females have reduced injury after myocardial ischemia and reperfusion injury. However, two large clinical trials, the women's health initiative (WHI) and the heart estrogen and progestin replacement study (HERS), found an increase in cardiovascular incidences in women taking hormone replacement therapy. The discrepancy between these data highlights the need for further research on the mechanism of estrogen in the cardiovascular system. Animal studies have demonstrated protective effects by endogenous estrogen (gender differences) and also by the administration of exogenous estrogen. In vivo studies suggest a possible anti-inflammatory mechanism of estrogen. Exogenous estrogen has been shown to have anti-oxidant activities. Pre-treatment with estrogen prior to myocardial ischemia and reperfusion causes a decrease in neutrophil infiltration into the irreversibly injured myocardium, decrease in C-reactive protein expression, and deposition of the membrane attack complex. This review will summarize the protection afforded by estrogen as well as discuss several possible mechanisms of protection for exogenous estrogen administration.
在绝经前，女性患心血管疾病的风险相对较低。然而，绝经后，风险几乎增加一倍，心血管疾病仍是女性的首要死因。在心血管疾病动物模型中的观察性试验和研究表明，雌性动物在心肌缺血和再灌注损伤后损伤减轻。然而，两项大型临床试验，即妇女健康倡议（WHI）和心脏雌激素与孕激素替代研究（HERS），发现接受激素替代疗法的女性心血管疾病发病率增加。这些数据之间的差异凸显了对雌激素在心血管系统中的作用机制进行进一步研究的必要性。动物研究已经证明内源性雌激素（性别差异）以及外源性雌激素给药具有保护作用。体内研究提示雌激素可能存在抗炎机制。外源性雌激素已被证明具有抗氧化活性。在心肌缺血和再灌注之前用雌激素预处理可导致不可逆损伤心肌中中性粒细胞浸润减少、C反应蛋白表达降低以及膜攻击复合物沉积减少。本综述将总结雌激素所提供的保护作用，并讨论外源性雌激素给药的几种可能保护机制。
