Anti-atherogenic functions of HDL are likely due to its mediation of reverse cholesterol transport and to its anti-oxidative and anti-inflammatory effects. Mounting evidence supports the concept that HDL may become dysfunctional and that this contributes to the development of atherosclerosis. The goal of our research is to define the mechanisms for HDL dysfunction in diseases associated with significantly increased risk of atherosclerotic cardiovascular disease, including familial hypercholesterolemia, chronic kidney disease and rheumatoid arthritis. A major hypothesis of our proposal is that excessive inflammatory and oxidative burden impair HDL atheroprotective functions, including cholesterol efflux capacity and anti-inflammatory and anti- oxidative effects. Core B will be an integral part of the PPG by providing both analytical services for analysis and isolation of lipoproteins and in vitro assays of HDL function in macrophages. The goal of Specific Aim 1 is to provide isolation and analysis of lipoproteins, HDL subfractions, and apoproteins. The Lipoprotein and HDL Function Core (Core B) will assist investigators by isolating lipoproteins and apoproteins, including apoAI and apoAII, for functional studies and analyses of protein modifications. The goal of Specific Aim 2 is to provide assays for HDL functions, including the promotion of cholesterol efflux and efferocytosis in macrophages and the control of inflammation and oxidation. Core B provides a number of services to investigators that require unique instrumentation and methodologies and demand rigorous standardization procedures. It would be costly, inefficient, and cumbersome to establish these procedures in individual investigator laboratories. The consolidation of these services into the Core B laboratory provides investigators with efficient, high quality, low-cost analyses. Another objective of Core B is to provide education and training to investigators, fellows, and research technicians on the science and methods of lipoprotein preparation and studies of HDL function.
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