HDL Function and Metabolism During Inflammation

炎症期间 HDL 的功能和代谢

• 批准号: 7406817
• 负责人: Deneys Rem Van Der Westhuyzen
• 金额: $ 141.63万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7406817
• 关键词: HDL; Function; Metabolism; During; Inflammation

DESCRIPTION (provided by applicant) Atherosclerosis is the leading cause of mortality in the western world. Unlike LDL, HDL levels are inversely correlated with the risk of atherosclerosis. HDL exerts its protective effect through several putative mechanisms, in large part through its ability to promote the so-called reverse cholesterol transport pathway. Atherosclerosis and inflammation share intimate associations and the atherosclerotic process exhibits features of a chronic inflammation. Inflammation is known to significantly alter HDL structure and composition, as well as plasma levels of HDL cholesterol and apolipoproteins, but the underlying mechanisms and the consequences of such changes on atherosclerotic disease are not understood. In studying the impact of HDL on atherosclerosis, it is therefore critical to understand how HDL may be modified as a result of inflammation, both systemically and within the inflammatory microenvironment of the atherosclerotic lesion. The Central Unifying Theme of this program project is an understanding of how inflammation alters HDL structure and metabolism and how such changes influence the development of atherosclerosis. The program comprises three inter-dependent and synergistic projects to address these questions: Project 1, "HDL structure and metabolism during inflammation" (PI, Frederick C. de Beer), will address how inflammation alters HDL remodeling through the actions of secreted phospholipases, SAA and CETP; Project 2, "Inflammation, HDL and Class B Scavenger Receptors" (PI, van der Westhuyzen) will determine how inflammation and SAA impact cellular lipid trafficking by Class B scavenger receptors; Project 3, "Macrophage cholesterol efflux during inflammation" (PI, Nancy R. Webb), will investigate the effect of inflammatory modifications of HDL on macrophage cholesterol efflux and atherosclerotic risk. The major goals of the program are to understand how HDL structure and metabolism are altered during inflammation and to determine how such changes influence HDL's function, particularly its roles in cellular cholesterol efflux and plasma cholesterol transport and its influence on atherosclerosis. The program is expected to make significant contributions towards elucidating how the inflammatory process affects HDL and cholesterol metabolism and the extent to which such effects impact atherosclerotic disease.

描述（由申请人提供） 动脉粥样硬化是西方世界死亡率的主要原因。与LDL不同，HDL水平与动脉粥样硬化的风险成反比。 HDL通过几种推定的机制发挥了保护作用，这在很大程度上是通过促进所谓的反向胆固醇运输途径的能力。 动脉粥样硬化和炎症具有亲密的关联，动脉粥样硬化过程表现出慢性炎症的特征。已知炎症会显着改变HDL的结构和组成，以及血浆的HDL胆固醇和载脂蛋白水平，但是尚不清楚这种变化对动脉粥样硬化疾病的潜在机制以及这种变化的后果。因此，在研究HDL对动脉粥样硬化的影响时，至关重要的是要了解如何在全身和炎症性微环境中因动脉粥样硬化病变的炎症而修饰HDL。该计划项目的主要统一主题是了解炎症如何改变HDL结构和代谢以及这种变化如何影响动脉粥样硬化的发展。该计划包括三个相互依赖和协同的项目来解决以下问题：项目1，“炎症期间的HDL结构和代谢”（PI，Frederick C. de Beer）将解决炎症如何通过分泌的磷脂酶，SAA和CETP的动作来改变HDL重塑HDL；项目2，“炎症，HDL和B级清道夫受体”（PI，van der Westhuyzen）将确定B级清除剂受体如何影响炎症和SAA如何影响细胞脂质运输；项目3，“炎症期间的巨噬细胞胆固醇外排”（PI，Nancy R. Webb）将研究HDL炎症修饰对巨噬细胞胆固醇外排和动脉粥样硬化风险的影响。该计划的主要目标是了解HDL结构和代谢在炎症过程中如何改变，并确定这种变化如何影响HDL的功能，尤其是其在细胞胆固醇外排和血浆胆固醇运输中的作用及其对动脉粥样硬化的影响。预计该计划将为阐明炎症过程如何影响HDL和胆固醇代谢以及这种影响影响动脉粥样硬化疾病的程度。