ORAL CONTRACEPTION AND ATHEROSCLEROSIS

虽然口服避孕药已经广泛使用了大约25年， 这些化合物对冠心病(CHD)风险的影响 目前仍不清楚。这很大程度上是由于缺乏对 雌激素和孕激素在动脉粥样硬化发病机制中的作用 而且，在存在动脉粥样硬化的情况下，临床上相关的血管舒缩因子 功能。 该项目的长期目标是利用一口井来确定- -非人类灵长类动物模型，雌激素和孕激素的影响 常用口服避孕药对动脉粥样硬化发病机制的研究 和先心病。具体目标是：1)确定一项 单独或在一定程度上联合使用避孕雌激素和孕激素 饮食诱导的冠状动脉粥样硬化；2)确定影响 雌激素和孕激素对早期卵巢功能参数的影响 动脉粥样硬化的形成，即低密度脂蛋白的摄取和降解，单核细胞对 内皮、内皮细胞周转；3)测定其影响 类固醇对血浆脂蛋白分布、异质性和组成的影响 类固醇引起的高密度脂蛋白成分的改变是否与 培养物对动脉粥样硬化程度或胆固醇流出的影响 胆固醇负荷的单核/巨噬细胞；4)确定 雌激素和孕激素在体内和体外的应用 培养的高胆固醇巨噬细胞胆固醇外流；以及5) 测定类固醇对内皮细胞介导的血管的影响 早期和晚期动脉粥样硬化的反应。 结果将提供一个重要的比较(非人类) 灵长类)更好地理解外源性雌激素作用的基础 和孕激素在冠心病发病机制上的作用，从而为建立 预防女性冠心病的方法。

While oral contraceptives have been in widespread use for about 25 years, the effects of these compounds on risk of coronary heart disease (CHD) remain unclear. This is due largely to a lack of basic investigation into effects of estrogens and progestins on the pathogenesis of atherosclerosis and, in the presence of atherosclerosis, clinically relevant vasomotor function. The long-term objective of this project is to determine, using a well- -characterized nonhuman primate model, effects of an estrogen and progestin commonly used in oral contraceptives on the pathogenesis of atherosclerosis and CHD. The specific aims are: 1) To determine the effects of a contraceptive estrogen and progestogen alone, or in combination, on extent of diet-induced coronary artery atherosclerosis; 2) to determine effects of the estrogen and progestogen on functional parameters of early atherogenesis, i.e., LDL uptake and degradation, monocyte adherence to endothelium, endothelial cell turnover; 3) to determine effects of the same steroids on plasma lipoprotein distribution, heterogeneity and composition, and whether steroid induced changes in HDL composition are associated with atherosclerosis extent or influence cholesterol efflux by cultured cholesterol laden monocyte/macrophages; 4) to determine direct effects of the estrogen and progestin administered both in vivo and in vitro on cholesterol efflux by cultured cholesterol laden macrophages; and 5) to determine effects of the steroids on endothelium mediated vascular responses in early and advanced atherosclerosis. The results will provide an important comparative (nonhuman primate) basis for understanding better the effects of exogenous estrogens and progestins on the pathogenesis of CHD and, thus, for establishing approaches to the prevention of CHD in women.