Division of Endocrinology, Department of Internal Medicine, University of Kentucky, Lexington, Kentucky 40536, USA.
Curr Opin Endocrinol Diabetes Obes. 2010 Apr;17(2):156-60. doi: 10.1097/MED.0b013e328337278b.
Inflammation and the concomitant acute phase response induce marked changes in the lipoprotein profile, particularly the high-density lipoprotein (HDL) fraction. The present review describes the transfer proteins and lipases that remodel HDL and regulate its plasma levels, discusses the changes occurring in their activities during inflammation, and the influence of this altered remodeling on HDL function. The review will also discuss the contribution of the ATP-binding-membrane-cassette transporters to the protective actions of HDL.
Studies using different models showed that remodeling of acute phase HDL in vitro generates pre-beta migrating particles capable of cholesterol efflux. Induction of the acute phase response in humans resulted in a reduction of HDL phospholipids without a change in HDL-cholesterol. However, the capacity of HDL to promote cholesterol efflux ex vivo was impaired. Studies with ATP-binding-membrane-cassette transporter A1 and ATP-binding-membrane-cassette transporter G1 knockout mice demonstrated anti-inflammatory roles for these transporters by virtue of reducing cell-membrane-free cholesterol and lipid raft content, thus attenuating proinflammatory signaling pathways.
It is well known that HDL has anti-inflammatory properties that are diminished during inflammation. Acute phase HDL contains serum amyloid A that can be liberated during remodeling by cholesteryl ester transfer protein and secretory phospholipase A2, or other inflammatory factors. The ability of serum amyloid A and apolipoprotein A-I to promote cholesterol efflux may confer protective effects during the acute phase response.
炎症及其伴随的急性期反应会引起脂蛋白谱的显著变化，尤其是高密度脂蛋白（HDL）部分。本综述描述了重塑 HDL 并调节其血浆水平的转运蛋白和脂酶，讨论了它们在炎症期间活性的变化，以及这种改变的重塑对 HDL 功能的影响。本综述还将讨论 ATP 结合膜盒转运蛋白对 HDL 保护作用的贡献。
使用不同模型的研究表明，体外急性相 HDL 的重塑会产生具有胆固醇外排能力的前-β迁移颗粒。在人类中诱导急性期反应会导致 HDL 磷脂减少而 HDL 胆固醇不变。然而，HDL 促进胆固醇外排的能力在体外受损。ATP 结合膜盒转运蛋白 A1 和 ATP 结合膜盒转运蛋白 G1 敲除小鼠的研究表明，这些转运蛋白通过减少细胞膜游离胆固醇和脂质筏含量，从而减弱促炎信号通路，具有抗炎作用。
众所周知，HDL 具有抗炎特性，在炎症期间会减弱。急性相 HDL 含有血清淀粉样蛋白 A，在胆固醇酯转移蛋白和分泌型磷脂酶 A2 或其他炎症因子的重塑过程中可以释放出来。血清淀粉样蛋白 A 和载脂蛋白 A-I 促进胆固醇外排的能力可能在急性期反应期间赋予保护作用。
