Hayek T, Oiknine J, Brook J G, Aviram M
Lipid Research Laboratory, Rambam Medical Center, Bruce Rappaport Faculty of Medicine, Technion, Israel.
Biochem Biophys Res Commun. 1994 Dec 15;205(2):1072-8. doi: 10.1006/bbrc.1994.2775.
The role of apo E in aspects of reverse cholesterol transport was studied in apolipoprotein E-deficient mice. These animals develop rampant atherosclerosis. The efflux of cholesterol from mouse peritoneal macrophages (MPM) was 40% lower when induced by high density lipoprotein (HDL) from apo E-deficient mice, compared to the effect of HDL from normal mice. On adding apo E to apo E-deficient HDL, cholesterol efflux from the macrophages increased by 35%, approaching the degree of efflux obtained with normal HDL. This HDL (normal or apo E-deficient)-induced cholesterol efflux was similar in peritoneal macrophages derived from both normal and apo E-deficient mice, suggesting that the HDL apo E rather than the macrophage apo E is responsible for the stimulation of cellular cholesterol efflux. On determining cholesterol efflux specifically from the macrophage plasma membrane, the level of efflux was similar for both HDL preparations, suggesting that apo E in HDL is important for cholesterol translocation to the plasma membrane, the initial step in reverse cholesterol transport. It is concluded that the enhanced atherosclerosis in apo E-deficient mice could be related, at least partly, to the impaired efflux of LDL derived cholesterol from macrophages of the arterial wall.
在载脂蛋白E缺乏的小鼠中研究了载脂蛋白E在胆固醇逆向转运方面的作用。这些动物会发展出严重的动脉粥样硬化。与正常小鼠的高密度脂蛋白（HDL）相比，载脂蛋白E缺乏小鼠的HDL诱导小鼠腹腔巨噬细胞（MPM）的胆固醇流出降低了40%。向载脂蛋白E缺乏的HDL中添加载脂蛋白E后，巨噬细胞的胆固醇流出增加了35%，接近正常HDL的流出程度。这种HDL（正常或载脂蛋白E缺乏）诱导的胆固醇流出在源自正常和载脂蛋白E缺乏小鼠的腹腔巨噬细胞中相似，表明HDL中的载脂蛋白E而非巨噬细胞中的载脂蛋白E负责刺激细胞胆固醇流出。在特异性测定源自巨噬细胞质膜的胆固醇流出时，两种HDL制剂的流出水平相似，表明HDL中的载脂蛋白E对于胆固醇转运至质膜（胆固醇逆向转运的第一步）很重要。得出的结论是，载脂蛋白E缺乏小鼠中动脉粥样硬化的加剧可能至少部分与动脉壁巨噬细胞中低密度脂蛋白衍生胆固醇的流出受损有关。
