Division of Biopharmaceutics, Leiden University, Leiden, The Netherlands.
Curr Pharm Des. 2010 May;16(13):1445-67. doi: 10.2174/138161210791051022.
Accumulation of cholesterol by macrophages, leading to their transformation into foam cells is a key event in the initiation of atherosclerosis. As maintenance of cholesterol homeostasis in macrophages is essential to prevent foam cell formation, mechanisms by which macrophages export cellular cholesterol have been intensively investigated in recent years. Several epidemiological studies have shown that plasma levels of high-density lipoprotein (HDL) cholesterol are inversely correlated with the risk of atherosclerosis. The protective effect of HDL against macrophage foam cell formation and atherosclerosis is primarily attributed to its role in reverse cholesterol transport (RCT), a process by which excess cholesterol in peripheral tissues is transported to the liver for excretion. The present review discusses current knowledge on the biological activities of the major apolipoproteins, enzymes, lipid transfer proteins, receptors, and lipid transporters associated with HDL function and levels. In addition, current views on the molecular mechanisms underlying the atheroprotective functions of HDL beyond promotion of RCT, including the anti-oxidant, anti-thrombotic, anti-inflammatory and anti-apoptotic properties of HDL are summarized.
巨噬细胞中胆固醇的积累，导致其转化为泡沫细胞，是动脉粥样硬化起始的一个关键事件。由于维持巨噬细胞中胆固醇的动态平衡对于防止泡沫细胞形成至关重要，因此近年来，人们已经深入研究了巨噬细胞中细胞胆固醇输出的机制。几项流行病学研究表明，血浆中高密度脂蛋白（HDL）胆固醇水平与动脉粥样硬化的风险呈负相关。HDL 对巨噬细胞泡沫细胞形成和动脉粥样硬化的保护作用主要归因于其在胆固醇逆转运（RCT）中的作用，即外周组织中多余的胆固醇被转运到肝脏排泄的过程。本文综述了与 HDL 功能和水平相关的主要载脂蛋白、酶、脂质转运蛋白、受体和脂质转运体的生物学活性的最新知识。此外，还总结了 HDL 除了促进 RCT 之外的抗动脉粥样硬化功能的分子机制的最新观点，包括 HDL 的抗氧化、抗血栓、抗炎和抗凋亡特性。
