Atorvastatin reduces CD68, FABP4, and HBP expression in oxLDL-treated human macrophages

Atorvastatin reduces CD68, FABP4, and HBP expression in oxLDL-treated human macrophages
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DOI:
10.1016/j.bbrc.2004.04.021
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发表时间:
2004-05-21
影响因子:
3.1
通讯作者:
Alegret, M
Alegret, M
中科院分区:
生物学4区
文献类型:
--
作者:
Llaverias, G;Noé, V;Alegret, M

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为了确定新的靶基因,可能有助于限制泡沫细胞的形成,我们分析了阿托伐他汀和氧化低密度脂蛋白(oxLDL)处理的人THP-1巨噬细胞的基因表达模式的变化。为此,我们使用了含有588个心血管相关cDNA的人cDNA阵列。暴露于oxLDL导致26个基因的差异表达,而与阿托伐他汀共孵育修改了29个基因的表达,与单独使用oxLDL治疗相比。通过定量RT-PCR和Western blot证实了可能与动脉粥样硬化过程相关的候选基因表达的变化。我们发现,阿托伐他汀阻止清道夫受体CD 68和脂肪酸结合蛋白4的表达增加引起的oxLDL。此外,阿托伐他汀降低HDL结合蛋白、载脂蛋白E和基质金属蛋白酶9的表达。这些发现对于理解他汀类药物对巨噬细胞的直接抗动脉粥样硬化作用是相关的。(C)2004年爱思唯尔公司All rights reserved.
With the aim of identifying new target genes that could contribute to limit foam cell formation, we analyzed changes in the pattern of gene expression in human THP-1 macrophages treated with atorvastatin and oxidized-LDL (oxLDL). To this end, we used a human cDNA array containing 588 cardiovascular-related cDNAs. Exposure to oxLDL resulted in differential expression of 26 genes, while coincubation with atorvastatin modified the expression of 29 genes, compared to treatment with oxLDL alone. Changes in the expression of candidate genes, potentially connected to the atherosclerotic process, were confirmed by quantitative RT-PCR and Western blot. We show that atorvastatin prevents the increase in the expression of scavenger receptor CD68 and that of fatty acid binding protein 4 caused by oxLDL. In addition, atorvastatin reduces the expression of HDL-binding protein, apolipoprotein E, and matrix metalloproteinase 9. These findings are relevant to understand the direct antiatherogenic effects of statins on macrophages. (C) 2004 Elsevier Inc. All rights reserved.