HIGH-DENSITY LIPOPROTEIN SPECIES--STRUCTURE AND ROLES

高密度脂蛋白（HDL）水平与 动脉粥样硬化 HDL似乎参与了胆固醇的清除 通过胆固醇的逆向运输排出体外。 准确的生物学 在这个过程中涉及的机制还没有很好地理解，至少在 这是由于HDL的复杂性。 这个问题的总体假设 HDL是一个离散亚种的集合，每个亚种 其可能具有独特的生物学功能。 该提案有三个 具体目标：（1）两个新定义的HDL亚组分，肝素结合 HDL和来源于人动脉粥样硬化主动脉斑块的HDL，将在 分离并表征。 这些脂蛋白将被分离， 选择性亲和免疫吸附，一种最低限度 对HDL结构的干扰。 (2)我们提出了一个模型， 前β HDL和α HDL亚组分之间的相互转化 与胆固醇通过HDL的运动有关。 具体方面 将通过体外孵育和颗粒 特征化 (3)确定HDL降解的主要部位 在体内，肝脏和肾脏，选择性地降解独特的HDL 亚种。 这些信息对于了解 HDL种类发挥作用的生化基础。 收集的资料 可用于增强HDL的表观保护作用， 动脉粥样硬化

High density lipoprotein (HDL) levels inversely correlate with atherosclerosis. HDL appear to be involved in the removal of cholesterol from the body by reverse cholesterol transport. The exact biological mechanisms involved in this process are not well understood, at least in part, due to the complexity of HDL. The overall hypothesis of this project is that HDL are a collection of discrete subspecies, each of which may have a unique biological function. This proposal has three specific aims: (1) Two newly defined HDL subfractions, heparin-binding HDL and HDL derived from human atherosclerotic aortic plaque, will be isolated and characterized. These lipoproteins will be isolated by selected affinity immunosorption, a technique which is minimally perturbing to HDL structure. (2) We have proposed a model suggesting that the interconversion between pre-beta HDL and alpha HDL subfractions is connected to the movement of cholesterol through HDL. Specific facets of this model will be investigated by in vitro incubations and particle characterization. (3) Determine if the major sites of HDL degradation in the body, the liver and kidney, selectively degrade unique HDL subspecies. Such information is essential to understanding the biochemical basis by which HDL species function. Information so gathered may be exploited to enhance the apparent protective effect of HDL against atherosclerosis.