Robust passive and active efflux of cellular cholesterol to a designer functional mimic of high density lipoprotein.
Robust passive and active efflux of cellular cholesterol to a designer functional mimic of high density lipoprotein.
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DOI：
10.1194/jlr.m054635
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发表时间：
2015-05
影响因子：
6.5
通讯作者：
Thaxton CS
中科院分区：
文献类型：
--
作者：
Luthi AJ;Lyssenko NN;Quach D;McMahon KM;Millar JS;Vickers KC;Rader DJ;Phillips MC;Mirkin CA;Thaxton CS
HDL支持巨噬细胞胆固醇流出的能力是其抗动脉粥样硬化作用的一个组成部分。增强这种能力，特别是当HDL胆固醇从巨噬细胞流出能力差时，代表了一种有前途的治疗策略。增强巨噬细胞胆固醇流出的一种方法是用HDL模拟物输注血液。先前，我们报道了HDL（fmHDL）的功能模拟物的合成，其由金纳米颗粒模板、磷脂双层和载脂蛋白A-I组成。在这项工作中，我们的特点的能力fmHDL支持成熟的细胞胆固醇流出模型细胞系和原代巨噬细胞的途径。fmHDL通过非介导（水性）和ABCG 1和I型B类清道夫受体（SR-BI）介导的扩散接受细胞胆固醇。此外，fmHDL holoparticle通过ABCA 1途径接受胆固醇和磷脂。这些结果表明，fmHDL支持天然HDL可用的所有胆固醇流出途径，因此，代表了一种有前途的用于增强巨噬细胞胆固醇流出的可输注治疗剂。fmHDL通过所有已知的胆固醇流出途径从细胞接受胆固醇：非介导的、ABCG 1和SR-BI介导的扩散以及通过ABCA 1。
The ability of HDL to support macrophage cholesterol efflux is an integral part of its atheroprotective action. Augmenting this ability, especially when HDL cholesterol efflux capacity from macrophages is poor, represents a promising therapeutic strategy. One approach to enhancing macrophage cholesterol efflux is infusing blood with HDL mimics. Previously, we reported the synthesis of a functional mimic of HDL (fmHDL) that consists of a gold nanoparticle template, a phospholipid bilayer, and apo A-I. In this work, we characterize the ability of fmHDL to support the well-established pathways of cellular cholesterol efflux from model cell lines and primary macrophages. fmHDL received cell cholesterol by unmediated (aqueous) and ABCG1- and scavenger receptor class B type I (SR-BI)-mediated diffusion. Furthermore, the fmHDL holoparticle accepted cholesterol and phospholipid by the ABCA1 pathway. These results demonstrate that fmHDL supports all the cholesterol efflux pathways available to native HDL and thus, represents a promising infusible therapeutic for enhancing macrophage cholesterol efflux. fmHDL accepts cholesterol from cells by all known pathways of cholesterol efflux: unmediated, ABCG1- and SR-BI-mediated diffusion, and through ABCA1.