NATIONAL RESEARCH AND DEMONSTRATION CTR. - ARTERIOSCLERO

国家研究和示范中心。

• 批准号: 3108493
• 负责人: ANTONIO M GOTTO
• 金额: $ 267.68万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-09-01 至 1991-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3108493
• 关键词: apolipoproteins; atherosclerosis; blood lipoprotein; blood lipoprotein metabolism; lipid structure; protein structure function

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.

本申请中提出的专业中心计划 动脉粥样硬化研究代表了一种多方面的方法 脂蛋白结构和代谢的研究。 总体目标 该计划旨在从分子水平上阐明脂质是如何分泌的 作为脂蛋白，这些物质的脂质和脱辅基蛋白成分如何 脂蛋白在颗粒内组织，这种组织是如何的 在新陈代谢过程中，脂蛋白如何被动和主动改变 与细胞相互作用并调节其功能，以及脂质最终如何 积聚在这些细胞中，产生血管疾病。 在这个 综合计划，具体项目将针对 阐明载脂蛋白E的氨基酸序列和 其信使RNA的核酸序列，结构的测定 载脂蛋白的特征赋予脂质结合特性和 增强卵磷脂的活性：胆固醇酰基转移酶，了解 脂质和载脂蛋白交换的动力学和热力学 转移，阐明参与代谢的结构改变 新生到成熟高密度脂蛋白的成熟，测定 不同高密度之间存在的代谢相互关系 脂蛋白群体，测量细胞对脂质的摄取率 低密度脂蛋白，并阐明其根本原因 高甘油三酯血症极低密度细胞代谢异常 脂蛋白。 执行拟议的研究将需要广泛的 物理（例如磁共振、光学和电子显微镜、 荧光、圆二色性、量热法、区带超速离心）、 化学（蛋白质测序、肽合成、脂质合成），以及 生物（细胞培养）技术。 这些研究活动将 由管理核心集成，并由数据支持 处理和仪器开发核心，脂蛋白分离和 分析服务核心，以及脱辅基蛋白分离和定量 核。 拟议的计划预计将提供新的、重要的 基本信息将有助于更清楚地了解 血浆脂蛋白的结构和代谢及其在血浆中的作用 动脉粥样硬化的发病机制。