Division of Molecular Medicine, Department of Medicine, Columbia University, 630 W 168th St, New York, NY 10032, USA.
Arterioscler Thromb Vasc Biol. 2010 Feb;30(2):139-43. doi: 10.1161/ATVBAHA.108.179283. Epub 2009 Oct 1.
Atherosclerosis has been characterized as a chronic inflammatory response to cholesterol deposition in arteries, but the mechanisms linking cholesterol accumulation in macrophage foam cells to inflammation are poorly understood. Macrophage cholesterol efflux occurs at all stages of atherosclerosis and protects cells from free cholesterol and oxysterol-induced toxicity. The ATP-binding cassette transporters ABCA1 and ABCG1 are responsible for the major part of macrophage cholesterol efflux to serum or HDL in macrophage foam cells, but other less efficient pathways such as passive efflux are also involved. Recent studies have shown that the sterol efflux activities of ABCA1 and ABCG1 modulate macrophage expression of inflammatory cytokines and chemokines as well as lymphocyte proliferative responses. In macrophages, transporter deficiency causes increased signaling via various Toll-like receptors including TLR4. These studies have shown that the traditional roles of HDL and ABC transporters in cholesterol efflux and reverse cholesterol transport are mechanistically linked to antiinflammatory and immunosuppressive functions of HDL. The underlying mechanisms may involve modulation of sterol levels and lipid organization in cell membranes.
动脉粥样硬化已被描述为胆固醇在动脉中沉积引起的慢性炎症反应，但胆固醇在巨噬细胞泡沫细胞中积累与炎症之间的联系机制尚不清楚。巨噬细胞胆固醇外流发生在动脉粥样硬化的所有阶段，可保护细胞免受游离胆固醇和氧化固醇诱导的毒性。ATP 结合盒转运体 ABCA1 和 ABCG1 负责巨噬细胞泡沫细胞中大部分的巨噬细胞胆固醇向血清或 HDL 的外流，但也涉及其他效率较低的途径，如被动外流。最近的研究表明，ABCA1 和 ABCG1 的固醇外流活性调节巨噬细胞炎症细胞因子和趋化因子的表达以及淋巴细胞的增殖反应。在巨噬细胞中，转运蛋白缺乏会导致各种 Toll 样受体（包括 TLR4）的信号转导增加。这些研究表明，HDL 和 ABC 转运体在胆固醇外流和胆固醇逆向转运中的传统作用与 HDL 的抗炎和免疫抑制功能在机制上是相关的。潜在的机制可能涉及调节细胞膜中固醇水平和脂质组织。
