HIGH DENSITY LIPOPROTEIN SPECIES--STRUCTURE AND ROLES

描述（改编自申请人摘要）：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，风险与高密度水平呈负相关 脂蛋白（HDL）。 高密度脂蛋白发挥保护作用的机制 效果尚未确定。 因此，需要了解更多关于 其结构和功能。 传统的HDL分离方法， 超离心，已经被证明掩盖了它们的分子形态 和生物功能。 相反，通过选择性亲和分离 免疫吸附保留了HDL的分子结构和功能 物种 这个项目将侧重于分离和表征本地 使用选择的亲和免疫吸附的HDL物种。 的体系结构 将确定各个物种。 几种新发现的HDL 蛋白质将被克隆和测序。 新分离的功能 物种将被研究，重点是他们的能力，参与 从细胞中回收胆固醇，它们的抗氧化特性及其 与动脉壁中发现的蛋白聚糖的物理相互作用。 特别注意的是一个新出现的HDL物种的研究， 67 kDa prebeta-1 HDL，一种似乎在细胞凋亡中起关键作用的颗粒， 从外周组织中回收胆固醇。 其可能的形成 在脂解过程中和在胆固醇酯的选择性摄取过程中 新发现的SR-BI受体将被探索，其行为在 将研究脂质代谢紊乱。 知识分子 高密度脂蛋白的形成可能导致新的预防和治疗策略 动脉粥样硬化性心脏病的研究， HDL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.