SPECIATION OF HDL AND LDL

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The aim of this project is to take advantage of major recent advances in knowledge of the structure-function relationships of plasma lipoproteins to characterize, in women, biological processes that are likely to predispose to coronary disease or to confer protection against it. Such knowledge, by identifying new risk factors, could lead to early identification of individuals at high risk and could also provide the basis for novel strategies of treatment designed to mitigate processes that contribute to atherogenesis, or to enhance those that are protective. Whereas ultracentrifugation appears to derange the native architecture of high density lipoproteins (HDL), a newly developed strategy of non- denaturing immunosorption permits the separation of seven to eight discrete species. Quantitative profiles of these newly discovered species will be measured in two hundred reproductive age and postmenopausal women. Functional roles of the individual species will be studied with respect to the transfer of cholesteryl esters to acceptor lipoproteins, a step critical to the cholesterol retrieval pathway. Deficient transfer of cholesteryl esters to low density lipoproteins (LDL) by HDL may underlie the phenomenon of hyperdense LDL, related in some studies to risk of coronary disease. This project will explore the relationship of HDL species distribution to this phenomenon. Oxidation of LDL may be critical to the development of arteriosclerotic heart disease. Significant inhibition of the process by HDL has been demonstrated. An objective of this study is the identification of all the HDL species responsible for this antioxidant effect and the mechanisms by which they act.