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 仍然不清楚。 这主要是由于缺乏对以下方面的基本调查： 雌激素和孕激素在动脉粥样硬化发病中的作用 并且，在存在动脉粥样硬化的情况下， 功能 该项目的长期目标是确定，使用良好的- - 表征的非人灵长类动物模型，雌激素和孕酮的作用 常用的口服避孕药对动脉粥样硬化的发病机制 还有CHD 具体目标是：1）确定一个 避孕雌激素和孕激素单独使用或联合使用， 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乳腺癌功能参数的影响 动脉粥样硬化形成，即，LDL摄取和降解，单核细胞粘附 内皮细胞，内皮细胞更新; 3）确定相同的效果 类固醇对血浆脂蛋白分布、异质性和组成的影响， 以及类固醇诱导的HDL成分变化是否与 动脉粥样硬化程度或影响胆固醇流出 胆固醇负载的单核细胞/巨噬细胞; 4）确定 体内和体外给药的雌激素和孕激素， 通过培养的胆固醇负载巨噬细胞的胆固醇流出;和5） 确定类固醇对内皮介导的血管的影响， 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） 灵长类动物）更好地了解外源性雌激素的作用的基础 和孕激素对冠心病发病机制的作用， 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.