Lipoprotein and HDL Function Core

摘要 高密度脂蛋白的抗动脉粥样硬化作用可能是由于它介导了胆固醇的反向运输 以及它的抗氧化和抗炎作用。越来越多的证据支持这一概念 高密度脂蛋白可能会功能失调，这会导致 动脉硬化。我们研究的目标是确定高密度脂蛋白功能障碍的机制。 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。一位少校 我们建议的假设是，过度的炎症和氧化负担会损害高密度脂蛋白 动脉粥样硬化的保护功能，包括胆固醇流出能力和抗炎和抗炎 氧化作用。核心B将通过提供这两种分析服务，成为PPG的组成部分 用于分析和分离巨噬细胞中的脂蛋白和体外测定高密度脂蛋白的功能。这个 特定目标1的目标是提供脂蛋白、高密度脂蛋白亚组分和 载脂蛋白。脂蛋白和高密度脂蛋白功能核心(核心B)将通过分离 脂蛋白和载脂蛋白，包括载脂蛋白AI和载脂蛋白II，用于功能研究和分析 蛋白质修饰。具体目标2的目标是提供对高密度脂蛋白功能的分析，包括 促进巨噬细胞胆固醇外流和胞吐作用及其调控 炎症和氧化。核心B为调查人员提供多项服务，这些服务需要 独特的仪器和方法，要求严格的标准化程序。它 在个人中建立这些程序将是昂贵、低效和麻烦的 调查员实验室。将这些服务整合到核心B实验室可提供 为调查人员提供高效、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高密度脂蛋白的功能研究。

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.