HDL Structure and Metabolism During Inflammation

炎症过程中 HDL 的结构和代谢

• 批准号: 7700655
• 负责人: FREDERICK C. DE BEER
• 金额: $ 32.02万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7700655
• 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.

动脉粥样硬化与炎症之间存在紧密的关联。动脉粥样硬化过程本身 慢性炎症的特征。此外，动脉粥样硬化的过程被深刻地加速了 慢性炎性疾病状态，例如类风湿关节炎。最近的第一和 在急性尿和 呼吸道感染。在影响脂质和 炎症过程中的脂蛋白是HDL的结构和代谢改变。在几乎所有物种中 HDL胆固醇和载脂蛋白A-L（APOA-L）显着降低。血清淀粉样蛋白 （SAA）由细胞因子巨大诱导，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性磷脂酶，尤其 磷脂酶A2（IIA SPLA2组），水解HDL表面磷脂具有显着代谢 后遗症。在短期内，可能需要这些变化才能生存，但是如果长期维持 有长期的病理后果。 该提议的论点是，急性相磷脂酶（IIA组SPLA2）协同作用 用胆固醇酯转移蛋白（CETP）推动载脂蛋白（SAA和APOA-L） 与球形HDL与不同的脂肪贫乏SAA或APOA-L实体相关（包括PrEP HDL） 和/甚至“免费”载脂蛋白。这个过程对HDL功能和 炎症期间的代谢。具体而言，脂肪贫乏的ApoA-L和SAA实体可能会促进 胆固醇外排同时容易受到加速分解代谢的影响。