Characterization of the cholesterol efflux of apolipoprotein E-containing high-density lipoprotein in THP-1 cells
Characterization of the cholesterol efflux of apolipoprotein E-containing high-density lipoprotein in THP-1 cells
复制标题
DOI：
10.1515/hsz-2018-0284
复制
发表时间：
2019-02-01
影响因子：
3.7
通讯作者：
Tozuka, Minoru
中科院分区：
文献类型：
--
作者：
Horiuchi, Yuna;Ohkawa, Ryunosuke;Tozuka, Minoru
高密度脂蛋白又称抗动脉粥样硬化脂蛋白，在大小、密度和组成上由不同的颗粒组成，表明不同的高密度脂蛋白亚类在特性和功能上存在差异。我们研究了含有载脂蛋白E(ApoE)的高密度脂蛋白，一个次要的高密度脂蛋白亚类，在高密度脂蛋白的胆固醇流出能力(CEC)中的作用，高密度脂蛋白是其主要的动脉粥样硬化保护功能。含载脂蛋白E的高密度脂蛋白的CEC与载脂蛋白E缺乏的高密度脂蛋白相似，但肝X受体激动剂刺激THP-1巨噬细胞后，前者的CEC增幅(1.48倍)明显高于后者(1.10倍)。在没有LXR激动剂的情况下，高密度脂蛋白中的主要载脂蛋白apoA-I和apoE之间的CEC没有差异，而经LXR激动剂处理后，apoA-I的CEC增加(4.25倍)大于apoE的(2.22倍)。此外，ATP结合盒转运体A1(ABCA1)的抑制剂格列本脲可显著降低LXR激动剂诱导的载脂蛋白E诱导的高密度脂蛋白的CEC增加。这些结果表明，与载脂蛋白E缺乏的高密度脂蛋白不同，含载脂蛋白E的高密度脂蛋白通过ABCA1参与胆固醇外流。
High-density lipoprotein (HDL), also known as antiatherogenic lipoprotein, consists of heterogeneous particles in terms of size, density and composition, suggesting differences among HDL subclasses in characteristics and functions. We investigated the role of apolipoprotein E (apoE)-containing HDL, a minor HDL subclass, in the cholesterol efflux capacity (CEC) of HDL, which is its predominant atheroprotective function. The CEC of apoE-ontaining HDL was similar to that of apoE-deficient HDL, but the former exhibited a greater rate increase (1.48-fold) compared to that of the latter (1.10-fold) by the stimulation of THP-1 macrophages with the Liver X Receptor (LXR) agonist. No difference in CEC was observed without the LXR agonist between apoA-I, the main apolipoprotein in HDL, and apoE, whereas the increase in CEC in response to treatment with the LXR agonist was greater for apoA-I (4.25-fold) than for apoE (2.22-fold). Furthermore, the increase in the CEC of apoE-containing HDL induced by the LXR agonist was significantly reduced by treatment with glyburide, an inhibitor of ATP-binding cassette transporter A1 (ABCA1). These results suggest that apoE-containing HDL, unlike apoE-deficient HDL, is involved in cholesterol efflux via ABCA1.