Human apolipoprotein A-II inhibits the formation of pre-beta high density lipoproteins
Human apolipoprotein A-II inhibits the formation of pre-beta high density lipoproteins
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DOI：
10.1016/s0005-2760(96)00102-6
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发表时间：
1996-11-11
期刊：
影响因子：
--
通讯作者：
Franceschini, G
中科院分区：
文献类型：
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作者：
Calabresi, L;Lucchini, A;Franceschini, G
在从 Intralipid 中分离出的富含甘油三酯的颗粒 (TGRP) 存在下，将天然和还原羧酰胺甲基化 (RCM) HDL(3) 与脂蛋白耗尽血浆组分 (LPDP) 一起孵育，研究人载脂蛋白 A-II (apoA-II) 在人高密度脂蛋白 (HDL) 重塑中的作用。 HDL(3)的还原-甲酰胺甲基化将二硫键连接的apoA-II二聚体完全转化为单体，而不影响HDL(3)的结构、组成和粒径分布。与 LPDP 和 TGRP 一起孵育后，未修饰的 HDL(3) 主要转化为大的 HDL(2) 颗粒（直径：9.90 +/- 0.07 nm），富含甘油三酯并耗尽胆固醇酯。 RCM-HDL(3) 被转换为大 HDL(2) (9.86 +/- 0.07 nm) 和小 HDL(7.53 +/- 0.06 nm) HDL(3)。这些小产品富含蛋白质且不含胆固醇，由两种不同的颗粒组成：一种具有前β迁移率，仅包含apoA-I；一种具有α迁移率，同时包含apoA-I和apoA-II。动力学研究表明，小前β-HDL(3) 的形成涉及一个两步过程，通过该过程，脂质成分的变化会导致脂蛋白结构/稳定性的改变，有利于载脂蛋白的解离和粒径的减小。这些发现表明，载脂蛋白结构是 HDL 重塑的主要决定因素，apoA-II 通过抑制小的、前 β 迁移 HDL 的形成，可能抵消 apoA-I 的抗动脉粥样硬化特性。
The role of human apolipoprotein A-II (apoA-II) in the remodeling of human high density lipoproteins (HDL) was investigated during incubation of native and reduced-carboxamidomethylated (RCM) HDL(3) with a lipoprotein-depleted plasma fraction (LPDP) in the presence of triglyceride-rich particles (TGRP) isolated from Intralipid. Reduction-carboxamidomethylation of HDL(3) entirely converts the disulfide-linked apoA-II dimers into monomers, without affecting the structure, composition and particle size distribution of HDL(3). Following incubation with LPDP and TGRP, unmodified HDL(3) are mainly converted into large, HDL(2) particles (diameter: 9.90 +/- 0.07 nm), enriched in triglycerides and depleted of cholesteryl esters. RCM-HDL(3) are converted into both large HDL(2) (9.86 +/- 0.07 nm) and small (7.53 +/- 0.06 nm) HDL(3). The small products are protein-rich and cholesterol-poor, and consist of two different particles: a component with pre-beta mobility, containing only apoA-I, and a component with alpha mobility, containing both apoA-I and apoA-II. Kinetic studies suggest that a two-step process is involved in the formation of small, pre beta-HDL(3), by which changes in lipid composition cause alterations in lipoprotein structure/stability, favoring the dissociation of apolipoproteins and reduction of particle size. These findings indicate that apolipoprotein structure is a major determinant of HDL remodeling, apoA-II potentially counteracting the anti-atherogenic properties of apoA-I by inhibiting the formation of small, pre-beta-migrating HDL.