HDL Structure and Metabolism During Inflammation

动脉粥样硬化和炎症之间存在着密切的联系。动脉粥样硬化过程本身就有 慢性炎症的特点。此外，动脉粥样硬化的进程被深刻地加速了 慢性炎症性疾病状态，如类风湿关节炎。最近较高的首发率和 随后观察到急性尿毒症和中风患者的心肌梗死和中风。 呼吸道感染。也许最值得注意的是过多的代谢变化会影响脂质和 炎症过程中的脂蛋白是高密度脂蛋白的结构和代谢变化。几乎在所有物种中 高密度脂蛋白-胆固醇和载脂蛋白A-L(apoA-L)明显降低。血清淀粉样蛋白A (SaA)是由细胞因子诱导的，甚至可以成为高密度脂蛋白的主要载脂蛋白。这个 同样的细胞因子同时诱导炎性磷脂酶，尤其是MA组的分泌物 降解高密度脂蛋白表面磷脂的磷脂酶A2(IIA sPLA2组) 后遗症。在短期内，这些变化可能是生存所必需的，但如果长期保持下去，可能会 会产生长期的病理性后果。 这一建议的主题是急性时相磷脂酶(IIA sPLA2组)协同作用 用胆固醇酯转运蛋白推动载脂蛋白(SAA和APOA-L) 结合球形高密度脂蛋白鉴别脂肪缺乏的SAA或载脂蛋白A-L实体(包括PREP高密度脂蛋白) 和/或甚至“游离”载脂蛋白。这一过程对高密度脂蛋白的功能和 炎症期间的新陈代谢。具体地说，脂类贫乏的载脂蛋白A-L和SAA实体可能促进 胆固醇外流，同时易受加速分解代谢的影响。

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.