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.
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