Lipoprotein and HDL Function Core

脂蛋白和HDL功能核心

• 批准号: 10544050
• 负责人: MACRAE F LINTON
• 金额: $ 23.76万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10544050
• 关键词: Anti-Inflammatory Agents; Antiatherogenic; Antiinflammatory Effect; Apolipoprotein A-II; Apoproteins; Atherosclerosis; Biological Assay; Cholesterol; Chronic Kidney Failure; Cost Analysis; Development; Disease; Familial Hypercholesterolemia; Functional disorder; Goals; Health Services Accessibility; High Density Lipoproteins; Impairment; Individual; Inflammation; Inflammatory; Laboratories; Lipoproteins; Macrophage; Mediation; Methodology; Methods; Post-Translational Protein Processing; Preparation; Procedures; Process; Protein Analysis; Research; Research Personnel; Research Project Grants; Rheumatoid Arthritis; Science; Services; Standardization; Training and Education; atheroprotective; atherosclerosis risk; cost; experimental study; human disease; in vitro Assay; instrumentation; method development; oxidation; reverse cholesterol transport

Summary Anti-atherogenic functions of HDL are likely due to its mediation of reverse cholesterol transport and to its anti-oxidative and anti-inflammatory effects. Mounting evidence supports the concept that HDL may become dysfunctional and that this contributes to the development of atherosclerosis. The goal of our research is to define the mechanisms for HDL dysfunction in diseases associated with significantly increased risk of atherosclerotic cardiovascular disease, including familial hypercholesterolemia, chronic kidney disease and rheumatoid arthritis. A major hypothesis of our proposal is that excessive inflammatory and oxidative burden impair HDL atheroprotective functions, including cholesterol efflux capacity and anti-inflammatory and anti- oxidative effects. Core B will be an integral part of the PPG by providing both analytical services for analysis and isolation of lipoproteins and in vitro assays of HDL function in macrophages. The goal of Specific Aim 1 is to provide isolation and analysis of lipoproteins, HDL subfractions, and apoproteins. The Lipoprotein and HDL Function Core (Core B) will assist investigators by isolating lipoproteins and apoproteins, including apoAI and apoAII, for functional studies and analyses of protein modifications. The goal of Specific Aim 2 is to provide assays for HDL functions, including the promotion of cholesterol efflux and efferocytosis in macrophages and the control of inflammation and oxidation. Core B provides a number of services to investigators that require unique instrumentation and methodologies and demand rigorous standardization procedures. It would be costly, inefficient, and cumbersome to establish these procedures in individual investigator laboratories. The consolidation of these services into the Core B laboratory provides investigators with efficient, high quality, low-cost analyses. Another objective of Core B is to provide education and training to investigators, fellows, and research technicians on the science and methods of lipoprotein preparation and studies of HDL function.

概括 HDL的抗动脉粥样硬化功能可能是由于其反向胆固醇转运的介导 以及其抗氧化和抗炎作用。安装证据支持这个概念 HDL可能会变得功能失调，这有助于发展 动脉粥样硬化。我们研究的目的是定义HDL功能障碍的机制 与动脉粥样硬化心血管疾病的风险显着增加有关的疾病， 包括家族性高胆固醇血症，慢性肾脏疾病和类风湿关节炎。专业 我们提案的假设是，过度炎症和氧化负担会损害HDL 动脉保护功能，包括胆固醇外排和抗炎和抗炎 氧化作用。核心B将通过提供两种分析服务来成为PPG不可或缺的一部分 用于分析和分离脂蛋白和巨噬细胞中HDL功能的体外测定。这 特定目的1的目标是提供脂蛋白，HDL亚构件和分析的隔离和分析 载蛋白。脂蛋白和HDL功能核心（核心B）将通过隔离 脂蛋白和亚蛋白，包括ApoAI和Apoaii，用于功能研究和分析 蛋白质修饰。特定目标2的目标是提供HDL功能的测定，包括 在巨噬细胞中促进胆固醇外排和肿瘤的肿瘤病以及 炎症和氧化。核心为需要的调查人员提供了许多服务 独特的仪器和方法和要求严格的标准化程序。它 在个人建立这些程序会很昂贵，效率低下且繁琐 研究人员实验室。将这些服务合并到核心B实验室提供 进行有效，高质量，低成本分析的研究人员。核心B的另一个目标是 向研究人员，研究员和研究技术人员提供教育和培训 和脂蛋白制备方法和HDL功能研究的方法。