Schmitz Gerd, Kaminski Wolfgang E
Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Franz-Josef-Strauss-Allee 11, Germany.
Curr Atheroscler Rep. 2002 May;4(3):243-51. doi: 10.1007/s11883-002-0026-2.
Macrophages play a central role in the initiation and progression of atherosclerotic lesions. In the nascent lesion, macrophages transform into foam cells through the excessive accumulation of cholesteryl esters. Dysfunctional lipid homeostasis in macrophages and foam cells ultimately results in the breakdown of membrane integrity and cell death. Studies within the past 2 years have implicated a defined subset of multispan transmembrane proteins, the ATP-binding cassette (ABC) transporters, in macrophage lipid homeostasis. The recent finding that ABCA1, beyond its function as a major regulator of plasma high-density lipoprotein metabolism, exerts significant antiatherosclerotic activities has provided the first direct evidence for the role of an ABC transporter in the pathogenesis of atherosclerosis.
巨噬细胞在动脉粥样硬化病变的发生和发展中起核心作用。在新生病变中,巨噬细胞通过胆固醇酯的过度积累转化为泡沫细胞。巨噬细胞和泡沫细胞中功能失调的脂质稳态最终导致膜完整性的破坏和细胞死亡。过去两年的研究表明,多跨膜蛋白的一个特定子集,即ATP结合盒(ABC)转运蛋白,参与了巨噬细胞脂质稳态。最近的发现表明,ABCA1除了作为血浆高密度脂蛋白代谢的主要调节因子发挥作用外,还具有显著的抗动脉粥样硬化活性,这为ABC转运蛋白在动脉粥样硬化发病机制中的作用提供了首个直接证据。