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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。大多数观察性研究支持这样的概念，即即使在LDL胆固醇升高的情况下，HDL胆固醇的理想水平与心血管疾病呈负相关。尽管如此，具有理想的HDL和升高的LDL水平的患者的子集具有增加的CVD风险。对一个家族和HDL清道夫受体SR-B1缺陷的敲除小鼠的研究概括了这种血脂异常（HDL和LDL升高）综合征伴CVD增加。这些研究人员假设，HDL和LDL升高的一部分人将是SR-B1缺乏症。将检查三个具体目的：1）表征HDL和LDL胆固醇升高的受试者中的脂蛋白组成和HDL-胆固醇酯的清除分数; 2）评估源自研究受试者的巨噬细胞中的SR-B1功能和表达; 3）鉴定研究受试者中SR-B1基因内的变体。这项工作的总体目标是提供新的见解SR-B1在人类血脂异常和动脉粥样硬化的作用，并挑战的概念，“理想的”HDL胆固醇水平总是心脏保护。

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.