Differential gene expression in the proximal neck of human abdominal aortic aneurysm
Differential gene expression in the proximal neck of human abdominal aortic aneurysm
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DOI：
10.1016/j.atherosclerosis.2013.12.017
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发表时间：
2014-03-01
期刊：
影响因子：
5.3
通讯作者：
Golledge, Jonathan
中科院分区：
文献类型：
--
作者：
Biros, Erik;Moran, Corey S.;Golledge, Jonathan
目的：腹主动脉瘤（AAA）是老年人群发病和死亡的常见原因，但AAA形成的机制仍不完全清楚。先前的人体研究集中于从AAA中心获得的活检，然而，在远离主扩张部位的相对正常的主动脉中也可能发生病理变化。本研究的目的是评估的基因表达谱的活检从颈部的人AAAs.Methods：我们进行了微阵列研究的主动脉瘤颈标本从14例AAA和8个控制主动脉标本从器官捐赠者。双重差异表达的基因进行了鉴定与多重检验校正。使用京都基因和基因组百科全书（KEGG）途径鉴定差异表达基因所代表的机制。结果：共鉴定出1047个差异表达基因，其中1047个基因在AAA瘤颈组织中表达差异。KEGG分析显示与免疫相关的基因显著上调。这些途径包括：精氨酸-细胞因子受体相互作用（P = 8.67*10（-12））、趋化因子信号传导途径（P = 5.76*10（-07））和抗原加工和呈递（P = 4.00*10（-04））。通过qPCR验证的差异表达基因的实例包括T细胞标志物CD 44（2.16倍上调，P = 0.008）和B细胞标志物CD 19（3.14倍上调，P = 0.029）。AAA颈部B细胞的存在被免疫组化证实。结论：免疫在AAA中的作用是有争议的。这项研究表明，免疫途径也上调内未扩张的主动脉近端的AAA。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Objective: Abdominal aortic aneurysm (AAA) represents a common cause of morbidity and mortality in elderly populations but the mechanisms involved in AAA formation remain incompletely understood. Previous human studies have focused on biopsies obtained from the center of the AAA however it is likely that pathological changes also occur in relatively normal appearing aorta away from the site of main dilatation. The aim of this study was to assess the gene expression profile of biopsies obtained from the neck of human AAAs.Methods: We performed a microarray study of aortic neck specimens obtained from 14 patients with AAA and 8 control aortic specimens obtained from organ donors. Two-fold differentially expressed genes were identified with correction for multiple testing. Mechanisms represented by differentially expressed genes were identified using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Some of the differentially expressed genes were validated by quantitative real-time PCR (qPCR) and immunohistochemistry.Results: We identified 1047 differentially expressed genes in AAA necks. The KEGG analysis revealed marked upregulation of genes related to immunity. These pathways included cytokine-cytokine receptor interaction (P = 8.67*10(-12)), chemokine signaling pathway (P = 5.76*10(-07)), and antigen processing and presentation (P = 4.00*10(-04)). Examples of differentially expressed genes validated by qPCR included the T-cells marker CD44 (2.16-fold upregulated, P = 0.008) and the B-cells marker CD19 (3.14-fold upregulated, P = 0.029). The presence of B-cells in AAA necks was confirmed by immunohistochemistry.Conclusions: The role of immunity in AAA is controversial. This study suggests that immune pathways are also upregulated within the undilated aorta proximal to an AAA. (C) 2014 Elsevier Ireland Ltd. All rights reserved.