DEFICIENCY OF THE HDL RECEPTOR, SR-BI, IN HUMANS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Most observational studies support the concept that the desirable levels of HDL cholesterol are inversely correlated to cardiovascular disease even in the presence of elevated LDL cholesterol. Nonetheless, a subset of patients with desirable HDL and elevated LDL levels are at increase risk for CVD. Studies in one family and knockout mice deficient in the HDL scavenger receptor, SR-B1, recapitulate this dyslipidemic (elevated HDL and LDL) syndrome with increased CVD. These investigators hypothesize that a subset of individuals with elevated HDL and LDL will be SR-B1 deficient. Three specific aims will be examined 1) characterize the lipoprotein composition and fractional clearance of HDL-cholesterol ester in subjects with elevated HDL and LDL cholesterol; 2)asses SR-B1 function and expression in macrophages derived from study subjects 3)identify variant within the SR-B1 gene in study subjects. The overarching goal of this work is to provide new insights into the role of SR-B1 in human dyslipidemia and atherosclerosis and challenge the concept that "desirable" HDL cholesterol levels are always cardioprotective.