DETERMINENTS OF CORONARY DISEASE

本项目的目标是鉴定新的生化 女性冠状动脉疾病的决定因素基于最近的进展， 对高密度脂蛋白的天然分子种类的理解 (HDL)HDL在胆固醇回收途径中的作用， 低密度脂蛋白（LDL）的量化亚形态， HDL抑制LDL氧化及其与性激素的关系 及其代谢物。 这样的知识可以提高我们的 能够识别有早发冠心病风险的女性， 导致新的预防和治疗战略， HDL种类在专门代谢作用中的功能。 分布 和结构的冠状动脉病变的妇女在风险，因为遗传 高胆固醇血症将通过定量冠状动脉血管造影术来研究， 冠状动脉内超声检查和超快速计算机断层扫描， 建立在横截面，发展病变的自然历史， 妇女和研究他们的关系，脂蛋白参数， 风险的预测者。 尽管超浓缩法长期用于HDL 研究扰乱了天然HDL物种的结构， 开发的选择性亲和免疫吸附技术表明， 存在7个或更多离散物种。 的定量分布 这些物种，HDL的能力，以防止氧化的LDL， 影响胆固醇酯向受体脂蛋白的转移， 将研究胆固醇回收途径的关键过程 冠心病的危险因素。 由于其潜在的 与HDL的胆固醇酯转移能力的关系， 将测量LDL的粒度分布。

The objective of this project is the identification of new biochemical determinants of coronary disease in women based on recent advances in understanding of the native molecular species of high density lipoproteins (HDL), the function of HDL in the retrieval pathway of cholesterol, the quantized subspeciation of low density lipoprotein (LDL), the ability of HDL to inhibit the oxidation of LDL and their relationship to sex hormones and their metabolites. Such knowledge can be expected to improve our ability to identify women at risk for premature coronary disease an could lead to new strategies of prevention and treatment that influence the function of HDL species in specialized metabolic roles. The distribution and architecture of coronary lesions in women at risk because of genetic hypercholesterolemia will be studied by quantitative coronary angiography, intracoronary ultrasonography and ultrafast computerized tomography to establish in cross section, the natural history of developing lesions in women and for study of their relationships to the lipoprotein parameters as predictors of risk. Whereas ultracentrifugation long employed for HDL studies deranges the architecture of native HDL species, the newly developed technique of selected affinity immunosorption demonstrates the existence of seven or more discrete species. The quantitative profile of these species, the ability of HDL to prevent the oxidation of LDL and to effect the transfer of cholesteryl esters to acceptor lipoproteins, a process critical to the retrieval pathway for cholesterol, will be studied as risk factors for coronary disease. Because of its potential relationship to the cholesteryl ester transfer capability of HDL, the particle size distribution of LDL will be measured.