异常修饰后高密度脂蛋白组分的改变对其功能的影响

Changes in biological functions of high-density lipoprotein after abnormal modification

高密度脂蛋白(high-density lipoprotein,HDL)是由载脂蛋白、脂质和多种功能蛋白所组成的结构复杂的多功能复合物。正常人血浆中的HDL主要通过胆固醇逆向转运(reverse cholesterol transport,RCT)发挥抗动脉粥样硬化(atherosclerosis,AS)作用,除此之外,HDL还有修复内皮细胞、抗炎、抗氧化和抗凋亡等作用。在全身炎症或代谢性疾病中,HDL组分被异常修饰,使其成分和功能发生改变,进而转变为功能失调HDL。功能失调HDL在成分和功能上均发生了改变:成分上载脂蛋白A-Ⅰ(apolipoprotein A-Ⅰ,apo A-Ⅰ)、对氧磷酶(paraoxonase,PON)和血小板活化因子乙酰水解酶(platelet activating factor acetylhydrolase,PAF-AH)等减少,而血清淀粉样蛋白A(serum amyloid A,SAA)、甘油三酯(triglyceride,TG)和氧化脂质等增加;功能上不仅失去了抗AS、抗炎、抗氧化等作用,反而具有促炎作用,可见盲目升高血浆HDL-C的含量并不一定能达到预期效果。因此了解异常修饰后HDL成分和功能的改变对深入了解功能失调HDL的致病机制具有重要的指导意义。

High-density lipoprotein （HDL） is composed of apolipoproteins, lipids and functional proteins. HDL protects against atherosclerosis （AS） by reverse cholesterol transport （RCT）. HDL inhibits the lipid oxidation, inflammation and restores endothelial function. During systemic inflammation or metabolic disorders, HDL can be modified abnormally and converted to a dysfunctional type, which results in the loss of anti-inflammatory factors including apolipoprotein A-I （apoA-I）, paraoxonase （PON） and platelet activating factor acetylhydrolase （PAF-AH）, and gains of pro-inflammatory factors such as serum amyloid A （SAA）, triglyceride （TG） and oxidative lipid. Therefore, understanding the changes in compositions and biological functions of dysfunctional HDL might help to comprehend its pathogenic mechanism.