Suppression of inflammatory signaling in monocytes from patients with coronary artery disease
Suppression of inflammatory signaling in monocytes from patients with coronary artery disease
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DOI：
10.1016/j.yjmcc.2008.10.029
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发表时间：
2009-02-01
影响因子：
5
通讯作者：
van Royen, Niels
中科院分区：
文献类型：
--
作者：
Schirmer, Stephan H.;Fledderus, Joost O.;van Royen, Niels
单核细胞和t细胞在动脉粥样硬化性冠状动脉疾病（CAD）的发展中起重要作用。对精心匹配的动脉粥样硬化患者和对照患者的循环单核细胞进行转录组分析，将有可能为动脉粥样硬化的病理生理学提供见解，并为诊断目的提供生物标志物。从因心绞痛症状而接受冠状动脉造影的患者中，我们仔细匹配了18例严重三支冠心病患者和13例没有冠心病血管造影征象的对照患者。所有患者均接受他汀类药物和阿司匹林治疗。可溶性icam水平升高表明动脉粥样硬化患者血管炎症增加。来自循环CD4+ t细胞、CD14+单核细胞、脂多糖刺激单核细胞和巨噬细胞的RNA进行全基因组表达分析。在CD14+单核细胞中，对照组患者很少有炎症基因过表达，而动脉粥样硬化患者则过度表达一组与kruppel相关的box - containing转录因子，这些转录因子参与基因表达的负调控。这些差异在lps刺激或向巨噬细胞分化后消失。未检测到t细胞转录组的一致性变化。大的个体间差异阻止了单个差异表达基因作为生物标志物的使用，而单细胞基因表达特征预测患者状态的准确率为84%。在这项对动脉粥样硬化性CAD循环细胞转录组的综合分析中，谨慎的患者匹配显示，不同单核细胞类型的转录活性仅存在微小差异。仅在动脉粥样硬化患者中检测到炎症基因表达的负反馈指示。当与临床症状和所服用的药物适当匹配时，循环细胞的转录组差异可能在个体患者对动脉粥样硬化性CAD的易感性中发挥的作用比迄今为止认为的要小。(C) 2008爱思唯尔公司版权所有。
Monocytes and T-cells play an important role in the development of atherosclerotic coronary artery disease (CAD). Transcriptome analysis of circulating mononuclear cells from carefully matched atherosclerotic and control patients will potentially provide insights into the pathophysiology of atherosclerosis and supply biomarkers for diagnostic purposes. From patients undergoing coronary angiography because of anginal symptoms, we carefully matched 18 patients with severe triple-vessel CAD to 13 control patients without angiographic signs of CAD. All patients were on statin and aspirin treatment. Elevated soluble-ICAM levels demonstrated increased vascular inflammation in atherosclerotic patients. RNA from circulating CD4+ T-cells, CD14+ monocytes, lipopolysaccharide-stimulated monocytes, and macrophages was subjected to genome-wide expression analysis. In CD14+ monocytes, few inflammatory genes were overexpressed in control patients, while atherosclerotic patients showed overexpression of a group of Kruppel-associated box - containing transcription factors involved in negative regulation of gene expression. These differences disappeared upon LPS-stimulation or differentiation towards macrophages. No consistent changes in Tcell transcriptomes were detected. Large inter-individual variability prevented the use of single differentially expressed genes as biomarkers, while monocyte gene expression signature predicted patient status with an accuracy of 84%. In this comprehensive analysis of circulating cell transcriptomes in atherosclerotic CAD, cautious patient matching revealed only small differences in transcriptional activity in different mononuclear cell types. Only an indication of a negative feedback to inflammatory gene expression was detected in atherosclerotic patients. Transcriptome differences of circulating cells possibly play less of a role than hitherto thought in the individual patient's susceptibility to atherosclerotic CAD, when appropriately matched for clinical symptoms and medication taken. (C) 2008 Elsevier Inc. All rights reserved.