Mazzone T, Lopez C, Bergstraesser L
Arteriosclerosis. 1987 Mar-Apr;7(2):191-6. doi: 10.1161/01.atv.7.2.191.
Chemically modified low density lipoproteins (LDL) are recognized by the macrophage scavenger receptor and can lead to substantial cholesteryl ester accumulation in cultured macrophages. Uptake of modified lipoproteins in vivo could contribute to foam cell formation during generation of the atherosclerotic plaque lesion. In the present study, modification of human pre-beta migrating very low density lipoprotein (VLDL) by acetylation led to recognition by the macrophage scavenger receptor as demonstrated in cross-competition experiments with acetylated LDL (ALDL). Recognition by this alternative binding site was associated with increased cholesterol delivery to human macrophages as assessed by suppression of LDL receptor activity, stimulation of cholesterol esterification rates, and accumulation of intracellular cholesteryl ester. Subfractionation of acetylated very low density lipoprotein (AVLDL) by ultracentrifugation in a discontinuous NaCl gradient demonstrated that AVLDL subfractions were equally effective in competing for 125I-ALDL uptake by macrophages when compared on the basis of particle number. These results suggest that modification of VLDL with subsequent recognition by the macrophage scavenger receptor may be a mechanism by which VLDL particles participate in macrophage cholesteryl ester overload.
化学修饰的低密度脂蛋白（LDL）可被巨噬细胞清道夫受体识别，并可导致培养的巨噬细胞中大量胆固醇酯蓄积。体内修饰脂蛋白的摄取可能在动脉粥样硬化斑块病变形成过程中促进泡沫细胞的形成。在本研究中，通过乙酰化修饰人前β迁移极低密度脂蛋白（VLDL），如在与乙酰化LDL（ALDL）的交叉竞争实验中所示，可导致其被巨噬细胞清道夫受体识别。通过抑制LDL受体活性、刺激胆固醇酯化率以及细胞内胆固醇酯蓄积评估，这种替代性结合位点的识别与向人巨噬细胞的胆固醇递送增加相关。在不连续NaCl梯度中通过超速离心对乙酰化极低密度脂蛋白（AVLDL）进行亚分级分离表明，基于颗粒数量比较时，AVLDL亚组分在竞争巨噬细胞摄取125I-ALDL方面同样有效。这些结果表明，VLDL的修饰以及随后被巨噬细胞清道夫受体识别可能是VLDL颗粒参与巨噬细胞胆固醇酯过载的一种机制。
