HDL Structure and Metabolism During Inflammation

炎症过程中 HDL 的结构和代谢

• 批准号: 7219726
• 负责人: FREDERICK C. DE BEER
• 金额: $ 32.69万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7219726
• 关键词: Acute; Adenovirus Vector; Affect; Animal Model; Apolipoproteins; Apolipoproteins A; Atherosclerosis; Binding; Blood Vessels; Catabolism; Charge; Cholesterol; Cholesterol Ester Transfer Proteins; Chronic; Deposition; Disease; Equilibrium; Generations; Hepatic; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Human; Hydrolysis; Inflammation; Inflammatory; Label; Lipase; Lipids; Lipoproteins; Metabolic; Metabolism; Movement; Myocardial Infarction; Nature; Patients; Phase; Phospholipase; Phospholipids; Plasma; Process; Rate; Reaction; Research Personnel; Respiratory Tract Infections; Rheumatoid Arthritis; Serum amyloid A protein; Site; Stroke; Structure; Surface; Testing; Time; Tissues; Transgenic Mice; Validation; base; cytokine; hepatic lipase; human PLA2G2A protein; in vivo; metabolic abnormality assessment; particle; programs; size; uptake; urinary

Intimate associations exist between atherosclerosis and inflammation. The atherosclerotic process itself has features of chronic inflammation. Furthermore, the process of atherosclerosis is profoundly accelerated by chronic inflammatory disease states such as rheumatoid arthritis. Recently higher rates of first and subsequent myocardial infarctions, as well as strokes, were observed in patients with acute urinary and respiratory infections. Perhaps most notable amongst the plethora of metabolic changes that affect lipid and lipoproteins during inflammation are the structural and metabolic alterations of HDL. In practically all species there is a significant decrease of HDL cholesterol and apolipoprotein A-l (apoA-l). Serum amyloid A protein (SAA) is dramatically induced by cytokines and can even become the major apolipoprotein of HDL. The same cytokines concomitantly induce the inflammatory phospholipases particularly group MA secretory phospholipase A2 (group IIA sPLA2) that hydrolyze HDL surface phospholipids with significant metabolic sequelae. In the short term these changes are likely required for survival, but if chronically maintained could have long-term pathological consequences. The thesis of this proposal is that the acute phase phospholipases (group IIA sPLA2) act in concert with cholesterol ester transfer protein (CETP) to propel the apolipoproteins (SAA and apoA-l) associated with spherical HDL to distinct lipid-poor SAA or apoA-l entities (including prep HDL) and/or even "free" apolipoproteins. This process hold major implications for HDL function and metabolism during inflammation. Specifically, the lipid-poor apoA-l and SAA entities likely promote cholesterol efflux whilst at the same time being susceptible to accelerated catabolism.

动脉粥样硬化和炎症之间存在密切联系。动脉粥样硬化过程本身