High-density lipoproteins (HDL) have been known since the 1960s to be associated with protection from atherosclerotic cardiovascular disease. However, the mechanisms of this protection are unclear. The extent to which HDL per se vs other correlated metabolic factors may mitigate atherosclerosis has been seriously questioned. In fact, new epidemiologic studies have found that in some clinical settings, very high HDL cholesterol levels correlate with increased atherosclerotic risk. Most importantly, over the past 2 decades, randomized clinical trials targeting HDL have failed to reproduce the usual epidemiologic inverse relation of HDL cholesterol to atherosclerotic events. In this roundtable discussion, we bring together 3 expert investigators working in the HDL field to elucidate questions of HDL function. One area of agreement is that reverse cholesterol transport remains a primary hypothesis for an anti-atherogenic role of HDL. Bioassays that measure cholesterol efflux capacity of HDL (or of apolipoprotein [apo] B-depleted plasma) have emerged as potentially accurate surrogates for reverse cholesterol transport. ApoA-I is the major functional apoprotein of HDL, but apoE- and apoC-III-containing subpopulations of HDL may have significant roles. Anti- and pro-inflammatory functions of various HDL particles, as well as the role of oxidative and other modifications, are gaining attention.

自 20 世纪 60 年代以来，人们就知道高密度脂蛋白 (HDL) 与预防动脉粥样硬化性心血管疾病有关。然而，这种保护的机制尚不清楚。HDL 本身与其他相关代谢因素相比可以在多大程度上减轻动脉粥样硬化一直受到严重质疑。事实上，新的流行病学研究发现，在某些临床环境中，极高的高密度脂蛋白胆固醇水平与动脉粥样硬化风险增加相关。最重要的是，在过去的 20 年中，针对 HDL 的随机临床试验未能重现 HDL 胆固醇与动脉粥样硬化事件之间常见的流行病学负相关关系。在本次圆桌讨论中，我们聚集了 3 位 HDL 领域的专家研究人员来阐明 HDL 功能的问题。一个共识是，胆固醇反向转运仍然是高密度脂蛋白抗动脉粥样硬化作用的主要假设。测量 HDL（或载脂蛋白 [apo] B 耗尽血浆）的胆固醇流出能力的生物测定已成为反向胆固醇转运的潜在准确替代品。ApoA-I 是 HDL 的主要功能性脱辅基蛋白，但含有 apoE 和 apoC-III 的 HDL 亚群可能具有重要作用。各种高密度脂蛋白颗粒的抗炎和促炎功能，以及氧化和其他修饰的作用，正在引起人们的关注。