NATIONAL RESEARCH AND DEMONSTRATION CTR. - ARTERIOSCLERO

在本申请中提出的专业中心的计划 动脉粥样硬化的研究代表了一种多方面的方法 脂蛋白结构和代谢的研究。总的目标是 本节目旨在从分子水平阐明脂类是如何分泌的。 作为脂蛋白，它们的脂质和载脂蛋白成分是如何 脂蛋白是在颗粒内组织起来的，这个组织是如何组织的 在代谢过程中被动和主动地改变，脂蛋白是如何 与细胞相互作用并调节它们的功能，以及脂质最终是如何 积聚在这些细胞中，产生血管疾病。在这 全面的计划，具体的项目将针对 载脂蛋白E和载脂蛋白E的氨基酸序列的阐明 其信使RNA的核酸序列，结构的测定 具有脂结合特性的载脂蛋白的特性和 提高卵磷脂：胆固醇酰基转移酶的活性，理解 脂类和载脂蛋白交换的动力学和热力学 转移，阐明伴随代谢的结构变化 新生至成熟高密度脂蛋白成熟度的测定 不同高密度之间存在的代谢相互关系 脂蛋白群体，测量细胞对脂类的摄取率 低密度脂蛋白，并阐明其潜在原因。 高甘油三酯血症极低密度症的细胞代谢异常 脂蛋白。执行拟议的研究将需要广泛的范围 物理(例如，磁共振、光和电子显微镜， 荧光、圆二色谱、量热法、分区超速离心法)、 化学(蛋白质测序、肽合成、脂类合成)，以及 生物(细胞培养)技术。这些研究活动将是 由管理核心集成，并将由数据支持 处理和仪器开发核心，一个脂蛋白分离和 分析服务核心，以及载脂蛋白分离和定量 核心。预计拟议的计划将提供新的和重要的 基本信息将使您更清楚地了解 血浆脂蛋白的结构和代谢及其在糖尿病发病中的作用 动脉粥样硬化的发病机制。

The program proposed in this application for a Specialized Center of Research in Atherosclerosis represents a multi-faceted approach to the study of lipoprotein structure and metabolism. The overall objective of this program is to elucidate on a molecular level how lipids are secreted as lipoproteins, how the lipid and apoprotein components of these lipoproteins are organized within the particle, how this organization is altered both passively and actively during metabolism, how lipoproteins interact with cells and regulate their function, and how lipids ultimately accumulate in these cells producing blood vessel disease. In this comprehensive program, specific projects will be directed toward the elucidation of the amino acid sequence of apolipoprotein E and of the nucleic acid sequence of its messenger RNA, determination of the structural features of apolipoproteins which confer lipid-binding properties and enhance the activity of lecithin:cholesterol acyltransferase, understanding the kinetics and thermodynamics of lipid and apolipoprotein exchange and transfer, elucidating the structural alterations which attend metabolic maturation of nascent to mature high density lipoproteins, determination of the metabolic interrelationships existing among the different high density lipoprotein populations, measuring the rate of cellular uptake of lipids in low density lipoproteins, and elucidating the underlying cause of the abnormal cellular metabolism of hypertriglyceridemic very low density lipoproteins. Execution of the proposed studies will require a wide range of physical (e.g. magnetic resonance, light and electron microscopy, fluorescence, circular dichroism, calorimetry, zonal ultracentrifugation), chemical (protein sequencing, peptide synthesis, lipid synthesis), and biological (cell culture) techniques. These research activities will be integrated by an Administrative Core and will be supported by a Data Processing and Instrument Development Core, a Lipoprotein Isolation and analytical Services Core, and an Apoprotein Isolation and Quantitation Core. The proposed program is expected to provide new and significant basic information that will lead to a clearer understanding of the structure and metabolism of plasma lipoproteins and their role in the pathogenesis of atherosclerosis.