Apolipoprotein A-I promotes cholesterol release and apolipoprotein E recruitment from THP-1 macrophage-like foam cells.
Apolipoprotein A-I promotes cholesterol release and apolipoprotein E recruitment from THP-1 macrophage-like foam cells.
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发表时间：
1999
影响因子：
6.5
通讯作者：
J. Bielicki;M. McCall;T. Forte
中科院分区：
文献类型：
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作者：
J. Bielicki;M. McCall;T. Forte
载脂蛋白E（apoE）由动脉巨噬细胞合成和分泌，而载脂蛋白A-I（apoA-I）存在于周围组织液中。两种载脂蛋白通过与细胞磷脂（PL）和胆固醇（UC）形成脂质复合物（nascent-HDL），从而促进胆固醇流出，在巨噬细胞胆固醇稳态中发挥重要作用。在这项研究中，我们评估了apoA-I和内源性产生的apoE介导细胞胆固醇募集的相对贡献。将THP-1人单核细胞分化（300 nm佛波醇二丁酸酯）成巨噬细胞，并通过用乙酰化LDL（50微克蛋白质/ml）加载胆固醇来产生巨噬细胞-泡沫细胞。ApoA-I（10 μ g/ml）在24 h内使巨噬细胞-泡沫细胞胆固醇酯消耗50%。与从巨噬细胞分离的复合物（UC/PL = 0.59 +/-0.08）相比，这种减少伴随着培养基中新生HDL的UC/PL摩尔比（UC/PL = 0.80 +/-0.15）的显著增加。apoA-I与巨噬泡沫细胞孵育后形成的nascent-HDL显著多于与巨噬细胞孵育后形成的nascent-HDL（70%）。与apoA-I不存在的孵育相比，在巨噬细胞和巨噬细胞泡沫细胞中分别观察到apoE蓄积介质促进了含有新生HDL的apoA-I的组装，其中增加了2倍和4倍。尽管中载脂蛋白E蓄积增加，但来自巨噬细胞和巨噬泡沫细胞的大多数（85%）颗粒（直径为11、9和7.4 nm）具有载脂蛋白A-I而不具有载脂蛋白E。ApoA-I加apoE颗粒（13-16 nm）也沿着少量apoE颗粒（19-20 nm）形成。然而，apoA-I仅颗粒的优势表明，与apoE的内源性产生相比，含有apoA-I的新生HDL的组装代表了细胞胆固醇募集的主要代谢途径。
Apolipoprotein E (apoE) is synthesized and secreted by arterial macrophages while apolipoprotein A-I (apoA-I) is present in surrounding interstitial fluids. Both apolipoproteins play important roles in macrophage cholesterol homeostasis by forming lipid complexes (nascent-HDL) with cellular phospholipids (PL) and cholesterol (UC) thereby promoting cholesterol efflux. In this study, we evaluated the relative contributions of apoA-I and endogenously produced apoE in mediating the recruitment of cellular cholesterol. THP-1 human monocytes were differentiated (300 nm phorbol dibutyrate) into macrophages and macrophage-foam cells were generated by cholesterol loading with acetylated LDL (50 microg protein/ml). ApoA-I (10 microg/ml) depleted macrophage-foam cell cholesteryl esters by 50% in 24 h. This reduction was accompanied by a significant increase in the UC/PL mole ratio of nascent HDL (UC/PL = 0.80 +/- 0.15) in the medium compared to complexes isolated from macrophages (UC/PL = 0.59 +/- 0.08). Significantly more (70%) nascent-HDL were formed in incubations of apoA-I with macrophage-foam cells than with macrophages. Medium apoE accumulation paralleled the assembly of apoA-I containing nascent HDL where 2- and 4-fold increases were observed with macrophages and macrophage-foam cells, respectively, compared to incubations in the absence of apoA-I. Despite the increase in medium apoE accumulation, a majority (85%) of particles (11, 9, and 7.4 nm in diameter) from macrophages and macrophage-foam cells possessed apoA-I without apoE. ApoA-I plus apoE particles (13-16 nm) were also formed along with a small quantity of apoE-only particles (19-20 nm). The predominance of apoA-I only particles indicates, however, that the assembly of apoA-I-containing nascent-HDL represents a major metabolic pathway of cellular cholesterol recruitment compared to the endogenous production of apoE.