HIGH-DENSITY LIPOPROTEIN SPECIES--STRUCTURE AND ROLES

高密度脂蛋白(HDL)水平与 动脉硬化。高密度脂蛋白似乎与胆固醇的去除有关。 通过逆向运输胆固醇从体内排出。确切的生物学特征 这一过程中涉及的机制还不是很清楚，至少在 第三部分，由于硬件描述语言的复杂性。对此的总体假设是 项目是高密度脂蛋白是一个离散亚种的集合，每个亚种 它可能具有独特的生物功能。这项建议有三个方面 具体目标：(1)两个新定义的高密度脂蛋白亚组分，肝素结合 高密度脂蛋白和高密度脂蛋白来源于人类动脉粥样硬化的主动脉斑块，将是 与世隔绝的，有特点的。这些脂蛋白将通过以下方式分离 选择性亲和免疫吸附，这是一种最低限度的 对高密度脂蛋白结构的干扰。(2)我们提出了一个模型，该模型认为 前β-高密度脂蛋白和α-高密度脂蛋白亚组分之间的相互转化 通过高密度脂蛋白与胆固醇的运动有关。特定方面 该模型的研究将通过体外孵化和粒子 人物刻画。(3)确定高密度脂蛋白降解的主要部位 在体内，肝脏和肾脏选择性地降解独特的高密度脂蛋白 亚种。这些信息对于理解 高密度脂蛋白物种发挥作用的生化基础。如此收集的信息 可能被用来增强高密度脂蛋白的明显保护作用 动脉硬化。

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.