HIGH DENSITY LIPOPROTEIN SPECIES--STRUCTURE AND ROLES

描述(改编自申请人的摘要)：鉴于 动脉硬化随着低密度水平的增加而增加 血浆中的脂蛋白，风险与高密度水平成反比 脂蛋白(Hdl)。高密度脂蛋白发挥保护性作用的机制 效果还没有确定。因此，我们需要更多地了解 它们的结构和功能。传统的分离高密度脂蛋白的方法， 超速离心，已被证明模糊了它们的分子形态。 和生物功能。相反，通过选择性亲和力进行分离 免疫吸附保留了高密度脂蛋白的分子结构和功能 物种。这个项目将专注于分离和描述原住民 利用选择性亲和免疫吸附的高密度脂蛋白的种类。的体系结构 具体的物种将会确定。几种新发现的高密度脂蛋白 蛋白质将被克隆和测序。新隔离的功能 将对物种进行研究，重点是它们参与 从细胞中回收胆固醇、其抗氧化性能及其作用 与动脉壁中发现的蛋白多糖的物理相互作用。 特别注意对一种新出现的高密度脂蛋白的研究 67 kDa前β-1高密度脂蛋白，一种似乎在 从外周组织中回收胆固醇。它可能的形成 在脂解和选择性摄取胆固醇酯的过程中 新发现的SR-BI受体将被探索，其行为将在 将对脂代谢紊乱进行研究。关于分子的知识 高密度脂蛋白的物种形成可能导致新的预防和治疗策略 动脉硬化性心脏病，并可能为理解 高密度脂蛋白在生物学中的其他作用。

DESCRIPTION (Adapted from applicant's abstract): Whereas the risk of arteriosclerosis increases with increasing levels of low density lipoproteins in plasma, risk is inversely related to levels of high density lipoproteins (HDL). The mechanisms by which HDL could exert a protective effect are not yet established. Therefore much more needs to be known about their structure and function. The traditional means of isolation of HDL, ultracentrifugation, has been shown to obscure their molecular speciation and biological functions. In contrast, isolation by selective affinity immunosorption preserves both the molecular architecture and function of HDL species. This project will focus on isolating and characterizing the native species of HDL using selected affinity immunosorption. The architectures of the individual species will be determined. Several newly discovered HDL proteins will be cloned and sequenced. The function of newly isolated species will be studied with emphasis on their ability to participate in the retrieval of cholesterol from cells, their antioxidant properties and their physical interaction with proteoglycans found in the artery wall. Particular attention is given to study of a newly emerging HDL species, the 67 kDa prebeta-1 HDL, a particle that appears to play a key role in the retrieval of cholesterol from peripheral tissues. Its possible formation during lipolysis and during the selective uptake of cholesteryl esters by the newly discovered SR-BI receptor will be explored and its behavior in disorders of lipid metabolism will be studied. Knowledge of the molecular speciation of HDL could lead to new strategies of prevention and treatment of arteriosclerotic heart disease and may provide insights for understanding other roles of HDL in biology.