Deckelbaum R J, Eisenberg S, Oschry Y, Granot E, Sharon I, Bengtsson-Olivecrona G
J Biol Chem. 1986 Apr 15;261(11):5201-8.
Cholesterol esters accumulating in human plasma high density lipoproteins (HDL) are important in conversion of HDL3 to larger HDL2. We studied whether mechanisms of removal of cholesterol esters from HDL might be important in a reverse direction, i.e. conversion of HDL2 to HDL3. Native HDL2 or HDL3 is incubated with very low density lipoproteins (VLDL) and lipoprotein-poor plasma (d greater than 1.21 g/ml) at 37 degrees C. After incubation, "modified" (M) VLDL, and HDL2 or HDL3 are reisolated by ultracentrifugation. In modified M-HDL2 or M-HDL3, triglyceride becomes the major core lipid as the triglyceride/cholesterol ester weight ratio increases 8-10-fold relative to native HDL. With only small changes in protein/phospholipid ratios in M-HDLs, the large decrease in cholesterol ester/protein ratios suggest net cholesterol ester loss from HDL. Quantitative recovery analyses prove that the cholesterol esters lost from HDL are transferred to M-VLDL, which is now richer in cholesterol ester and poorer in triglyceride. These substantial exchanges of HDL lipids are not associated by significant transfer of HDL apoproteins but are dependent on neutral lipid transfer factors present in human lipoprotein-poor plasma (d greater than 1.21 g/ml). Similar results are obtained when purified core lipid transfer protein replaces d greater than 1.21 g/ml plasma in these incubations. After depletion of cholesterol ester from HDL, most but not all, exchanged triglyceride can be removed by lipolysis with either hepatic or lipoprotein lipase, resulting in a post-lipolysis HDL2 with an increased triglyceride content relative to normal HDL. With successive incubations with VLDL, and core lipid transfer factors, HDL2 loses more than two-thirds of its cholesterol esters. After lipolysis of acquired triglyceride, HDL2 is remodeled, in both composition and flotation parameters, toward HDL3.
积聚在人血浆高密度脂蛋白（HDL）中的胆固醇酯在HDL3转化为更大的HDL2过程中起重要作用。我们研究了HDL中胆固醇酯的清除机制是否可能在相反方向上起重要作用，即HDL2转化为HDL3。将天然HDL2或HDL3与极低密度脂蛋白（VLDL）和脱脂血浆（d大于1.21 g/ml）在37℃孵育。孵育后，通过超速离心重新分离“修饰的”（M）VLDL以及HDL2或HDL3。在修饰的M-HDL2或M-HDL3中，随着甘油三酯/胆固醇酯重量比相对于天然HDL增加8至10倍，甘油三酯成为主要的核心脂质。M-HDL中蛋白质/磷脂比仅有微小变化，胆固醇酯/蛋白质比大幅下降表明HDL中胆固醇酯净损失。定量回收分析证明，从HDL中损失的胆固醇酯转移至M-VLDL，后者现在胆固醇酯含量更高而甘油三酯含量更低。HDL脂质的这些大量交换与HDL载脂蛋白的显著转移无关，但依赖于人脱脂血浆（d大于1.21 g/ml）中存在的中性脂质转移因子。当在这些孵育中用纯化的核心脂质转移蛋白替代d大于l.21 g/ml血浆时，可获得相似结果。HDL中胆固醇酯耗尽后，大部分但并非全部交换的甘油三酯可通过肝脂酶或脂蛋白脂酶的脂解作用去除，导致脂解后HDL2的甘油三酯含量相对于正常HDL增加。随着与VLDL和核心脂质转移因子的连续孵育，HDL2损失超过其三分之二的胆固醇酯。在获得的甘油三酯进行脂解后，HDL2在组成和漂浮参数方面都向HDL3重塑。
