Department of Medicine, David Geffen School of Medicine, UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095-1679, USA.
Nat Rev Cardiol. 2011 Apr;8(4):222-32. doi: 10.1038/nrcardio.2010.222. Epub 2011 Feb 8.
The lipoprotein HDL has two important roles: first, it promotes reverse cholesterol transport, and second, it modulates inflammation. Epidemiological studies show that HDL-cholesterol levels are inversely correlated with the risk of cardiovascular events. However, many patients who experience a clinical event have normal, or even high, levels of HDL cholesterol. Measuring HDL-cholesterol levels provides information about the size of the HDL pool, but does not predict HDL composition or function. The main component of HDL, apolipoprotein A-I (apo A-I), is largely responsible for reverse cholesterol transport through the macrophage ATP-binding cassette transporter ABCA1. Apo A-I can be damaged by oxidative mechanisms, which render the protein less able to promote cholesterol efflux. HDL also contains a number of other proteins that are affected by the oxidative environment of the acute-phase response. Modification of the protein components of HDL can convert it from an anti-inflammatory to a proinflammatory particle. Small peptides that mimic some of the properties of apo A-I have been shown in preclinical models to improve HDL function and reduce atherosclerosis without altering HDL-cholesterol levels. Robust assays to evaluate the function of HDL are needed to supplement the measurement of HDL-cholesterol levels in the clinic.
高密度脂蛋白（HDL）在脂蛋白中有两个重要作用：一是促进胆固醇逆向转运，二是调节炎症。流行病学研究表明，HDL 胆固醇水平与心血管事件的风险呈负相关。然而，许多经历临床事件的患者的 HDL 胆固醇水平正常，甚至偏高。测量 HDL 胆固醇水平可提供有关 HDL 池大小的信息，但不能预测 HDL 的组成或功能。HDL 的主要成分载脂蛋白 A-I（apo A-I）在很大程度上通过巨噬细胞三磷酸腺苷结合盒转运体 ABCA1 负责胆固醇的逆向转运。apo A-I 可被氧化机制破坏，使其更难以促进胆固醇外流。HDL 还含有许多其他受急性期反应氧化环境影响的蛋白质。HDL 蛋白成分的修饰可将其从抗炎颗粒转化为促炎颗粒。在临床前模型中，模拟 apo A-I 某些特性的小肽已被证明可改善 HDL 功能并减少动脉粥样硬化，而不会改变 HDL 胆固醇水平。需要功能齐全的 HDL 检测方法来补充临床中 HDL 胆固醇水平的测量。
