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.

总结 HDL的抗动脉粥样硬化功能可能是由于其介导的胆固醇逆向转运 以及其抗氧化和抗炎作用。越来越多的证据支持了 HDL可能变得功能失调，这有助于发展 动脉粥样硬化我们研究的目的是确定HDL功能障碍的机制， 与动脉粥样硬化性心血管疾病风险显著增加相关的疾病， 包括家族性高胆固醇血症、慢性肾病和类风湿性关节炎。一个主要 我们提出假设是过度的炎症和氧化负荷损害HDL 动脉粥样硬化保护功能，包括胆固醇流出能力和抗炎和抗 氧化作用。核心B将通过提供两种分析服务， 用于脂蛋白的分析和分离以及巨噬细胞中HDL功能的体外测定。的 具体目标1的目标是提供脂蛋白、HDL亚组分和 脱辅基蛋白脂蛋白和HDL功能核心（核心B）将通过分离 脂蛋白和载脂蛋白，包括apoAI和apoAII，用于功能研究和分析， 蛋白质修饰Specific Aim 2的目标是提供HDL功能的测定，包括 促进巨噬细胞中胆固醇流出和巨噬细胞增多， 炎症和氧化。核心B为研究者提供了许多服务， 独特的仪器和方法，并要求严格的标准化程序。它 将是昂贵的，低效的，繁琐的，建立这些程序在个人 实验室调查员将这些服务整合到核心B实验室， 研究人员提供高效、高质量、低成本的分析。核心B的另一个目标是 为研究人员、研究员和研究技术人员提供科学方面的教育和培训 以及脂蛋白的制备方法和HDL功能的研究。