Altered expression of inflammation-related genes in human carotid atherosclerotic plaques
Altered expression of inflammation-related genes in human carotid atherosclerotic plaques
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DOI：
10.1016/j.atherosclerosis.2011.10.022
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发表时间：
2012-01-01
期刊：
影响因子：
5.3
通讯作者：
Salvatore, Francesco
中科院分区：
文献类型：
--
作者：
Di Taranto, Maria Donata;Morgante, Alberto;Salvatore, Francesco
目的：炎症是动脉粥样硬化发生和发展的关键过程，但其潜在的分子机制仍很不清楚。我们对动脉粥样硬化斑块进行了广泛的表达研究，以确定参与动脉粥样硬化的炎症途径。方法：我们研究了11个人颈动脉斑块及其相应的邻近区域和7个来自不同受试者的对照动脉。用TaqMan低密度阵列人炎性板法研究92个基因的表达。结果：92个基因中，有44个基因(48%)在不同组织中的表达水平有显著差异(13个上调，31个下调)。失调基因编码属于不同功能类别的分子，尽管其中大多数编码与二十烷类化合物合成途径有关的酶。在oxLDL和TNF-α刺激下，人主动脉内皮细胞和血管内皮细胞中PTGIS和PTGIR基因表达降低。结论：本研究不仅揭示了人类病变中的几个异常基因，而且揭示了参与二十烷类合成途径的基因在动脉粥样硬化发展过程中的作用。氧化低密度脂蛋白处理后PTGIS和PTGIR表达的降低反映了动脉粥样硬化病变中与对照动脉相比的mRNA水平的降低，这表明氧化在动脉粥样硬化发展过程中对PTGIS和PTGIR的调节具有重要意义。(C)2011爱思唯尔爱尔兰有限公司。保留所有权利。
Objective: Inflammation is a pivotal process in atherosclerosis development and progression, but the underlying molecular mechanisms remain largely obscure. We have conducted an extensive expression study of atherosclerotic plaques to identify the inflammatory pathways involved in atherosclerosis.Methods: We studied 11 human carotid plaques, their respective adjacent regions and 7 control arteries from different subjects. Expression of 92 genes was studied by TaqMan low-density array human inflammation panel. Human aortic endothelial and smooth muscle cells were used for in vitro experiments.Results: The mRNA levels of 44/92 genes (48%) differed significantly between the tissues examined (13 up-regulated and 31 down-regulated). Dysregulated genes encode molecules belonging to different functional classes although most of them encode enzymes involved in the eicosanoid synthesis pathway. The expression of PTGIS and PTGIR genes was decreased in human aortic endothelial and smooth muscle cells stimulated with oxLDL and TNF-alpha.Conclusions: This study not only reveals several dysregulated genes in human lesions but also focuses the role played by the genes involved in the eicosanoid synthesis pathway during atherosclerotic development. The decrease of PTGIS and PTGIR expression after oxLDL treatment mirrors the decreased mRNA levels in atherosclerotic lesions versus control arteries, which suggests that oxidation is important for PTGIS and PTGIR regulation in human vessel cells during atherosclerosis development. (C) 2011 Elsevier Ireland Ltd. All rights reserved.