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关联。动脉粥样硬化过程本身 慢性炎症的特点。此外，动脉粥样硬化的进程大大加速 慢性炎症性疾病，例如类风湿性关节炎。最近首次和的比率较高 在患有急性尿路和中风的患者中观察到随后的心肌梗塞以及中风。 呼吸道感染。也许在影响脂质和代谢的大量代谢变化中最值得注意的是 炎症期间的脂蛋白是HDL的结构和代谢改变。几乎所有物种 HDL 胆固醇和载脂蛋白 A-1 (apoA-1) 显着降低。血清淀粉样A蛋白 (SAA) 受到细胞因子的显着诱导，甚至可以成为 HDL 的主要载脂蛋白。这 相同的细胞因子同时诱导炎症磷脂酶，特别是 MA 分泌酶 磷脂酶 A2（IIA sPLA2 组），水解 HDL 表面磷脂，具有显着的代谢作用 后遗症。在短期内，这些变化可能是生存所必需的，但如果长期维持，可能会 产生长期的病理后果。 该提案的论点是急性期磷脂酶（IIA sPLA2 组）协同作用 与胆固醇酯转移蛋白 (CETP) 一起推动载脂蛋白（SAA 和 apoA-l） 与球形 HDL 相关，形成不同的贫脂 SAA 或 apoA-l 实体（包括制备 HDL） 和/或什至“游离”载脂蛋白。这个过程对 HDL 功能和 炎症期间的新陈代谢。具体来说，缺乏脂质的 apoA-l 和 SAA 实体可能会促进 胆固醇外流，同时容易加速分解代谢。