动脉粥样硬化中胆固醇外流的研究进展

Research Advances of Cholesterol Efflux in Atherosclerosis

三磷酸腺苷结合盒转运体A1(ABCA1)、三磷酸腺苷结合盒转运体G1(ABCG1)和B族Ⅰ型清道夫受体(SR-BⅠ)介导的胆固醇外流是巨噬细胞内3条主要的胆固醇外流途径,对维持细胞内胆固醇动态平衡至关重要,其中转运体的功能及其表达的调节、胞外接受体的数量和活性等对细胞内胆固醇外流效率有重要的决定作用.最新研究发现,动脉粥样硬化(As)病变中出现的脂类蓄积、炎症、氧化应激、缺氧和胰岛素抵抗等病理情况,显著影响胆固醇转运体的表达,进而影响胆固醇外流及As的发生发展.本文主要针对As病变细胞内各胆固醇外流途径的作用及常伴随的脂类蓄积、炎症、氧化应激、缺氧和胰岛素抵抗现象,对胆固醇转运体表达调节的最新进展做一综述,以期为As治疗提供新理论依据和药物靶点,推动As治疗方法的发展.

The major pathways of cholesterol efflux from macrophages are the transmembrane transports mediated by membrane proteins involved ATP-binding cassette transporters A1,ATP-binding cassette transporters G1 and scavenger receptor class B typeⅠ,which are essential for cellular cholesterol homeostasis.The efficiency of cellular cholesterol efflux is determined by the activity of membrane transporters and regulation of their expression,the quantity and quality of extracellular acceptors and so on.Recent advances indicate that conditions locally in the atherosclerotic lesion,including lipids accumulation,inflammation,oxidative stress,hypoxia and insulin resistance,critically influence the expression of cholesterol transporters,which is in line affects the happen and progress of atherosclerosis associated with a change of cholesterol efflux.This review focuses on the current views on the relative roles of different cellular cholesterol efflux pathways,and the regulation on transporters of lipids accumulation,inflammation,oxidative stress,hypoxia and insulin resistence,which often accompany with the happen of atherosclerotic lesion,aiming at providing new theoretical evidence and drug targets to promote the development of therapies on atherosclerosis.