Phillips M C, Gillotte K L, Haynes M P, Johnson W J, Lund-Katz S, Rothblat G H
Biochemistry Department, MCP-Hahnemann School of Medicine, Allegheny University of the Health Sciences, Philadelphia, PA 19129, USA.
Atherosclerosis. 1998 Apr;137 Suppl:S13-7. doi: 10.1016/s0021-9150(97)00312-2.
The participation of HDL in the reverse cholesterol transport (RCT) from peripheral cells to the liver is critical for the antiatherogenic properties of this lipoprotein. Experimental results showing that efflux of cholesterol from cells growing in culture is mediated by HDL and lipoprotein particles containing apo A-I, in particular, support this conclusion. A bidirectional flux of unesterified cholesterol molecules between the plasma membrane of cells and HDL particles in the extracellular medium occurs. Net efflux of cholesterol mass from the cells involves passive diffusion of cholesterol molecules through the aqueous phase and down their concentration gradient between the membrane and HDL; the concentration gradient is maintained by LCAT-mediated esterification of cholesterol molecules in the HDL particles. Fully lipidated apo A-I is important in promoting this aqueous diffusion mechanism because it: (1) acts as a cofactor for LCAT; and (2) solubilizes phospholipid into small HDL-sized particles that are efficient at absorbing cholesterol molecules diffusing away from the cell surface. Apo A-I also exists in an incompletely lipidated state in plasma. Apo A-I molecules in this state are able to solubilize phospholipid and cholesterol from the plasma membrane of cells. This membrane-microsolubilization process is enhanced by enrichment of the plasma membrane with cholesterol and is the mechanism by which pre-beta-HDL particles in the extracellular medium remove cholesterol and phospholipid from cells. The relative contributions in vivo of the aqueous diffusion and membrane-microsolubilization mechanisms of apo A-I-mediated cell cholesterol efflux are not predicted readily from cell culture experiments. Confounding issues are the variations with cell type and the dependence on the degree of cholesterol loading of the cell plasma membrane.
高密度脂蛋白（HDL）参与胆固醇从外周细胞到肝脏的逆向胆固醇转运（RCT），这对于该脂蛋白的抗动脉粥样硬化特性至关重要。实验结果表明，培养的细胞中胆固醇的流出是由HDL和含有载脂蛋白A-I的脂蛋白颗粒介导的，这一结果尤其支持了这一结论。细胞的质膜与细胞外介质中的HDL颗粒之间存在未酯化胆固醇分子的双向流动。细胞中胆固醇质量的净流出涉及胆固醇分子通过水相的被动扩散以及沿着其在膜和HDL之间的浓度梯度扩散；该浓度梯度通过HDL颗粒中卵磷脂胆固醇酰基转移酶（LCAT）介导的胆固醇分子酯化得以维持。完全脂化的载脂蛋白A-I在促进这种水相扩散机制中很重要，因为它：（1）作为LCAT的辅因子；（2）将磷脂溶解成小的HDL大小的颗粒，这些颗粒能有效吸收从细胞表面扩散出去的胆固醇分子。载脂蛋白A-I在血浆中也以不完全脂化的状态存在。处于这种状态的载脂蛋白A-I分子能够从细胞质膜中溶解磷脂和胆固醇。这种膜微溶解过程通过质膜中胆固醇的富集而增强，并且是细胞外介质中的前β-HDL颗粒从细胞中去除胆固醇和磷脂的机制。载脂蛋白A-I介导的细胞胆固醇流出的水相扩散和膜微溶解机制在体内的相对贡献不能轻易从细胞培养实验中预测。混杂的问题包括细胞类型的差异以及对细胞质膜胆固醇负载程度的依赖性。
