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人类腹主动脉瘤与主动脉闭塞性疾病中的基因差异表达

Differential gene expression in human abdominal aortic aneurysm and aortic occlusive disease.

作者信息

Biros Erik, Gäbel Gabor, Moran Corey S, Schreurs Charlotte, Lindeman Jan H N, Walker Philip J, Nataatmadja Maria, West Malcolm, Holdt Lesca M, Hinterseher Irene, Pilarsky Christian, Golledge Jonathan

机构信息

The Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia.

Department of Vascular and Endovascular Surgery, Ludwig-Maximillian University, Munich, Germany.

出版信息

Oncotarget. 2015 May 30;6(15):12984-96. doi: 10.18632/oncotarget.3848.

Abstract

Abdominal aortic aneurysm (AAA) and aortic occlusive disease (AOD) represent common causes of morbidity and mortality in elderly populations which were previously believed to have common aetiologies. The aim of this study was to assess the gene expression in human AAA and AOD. We performed microarrays using aortic specimen obtained from 20 patients with small AAAs (≤ 55mm), 29 patients with large AAAs (> 55mm), 9 AOD patients, and 10 control aortic specimens obtained from organ donors. Some differentially expressed genes were validated by quantitative-PCR (qRT-PCR)/immunohistochemistry. We identified 840 and 1,014 differentially expressed genes in small and large AAAs, respectively. Immune-related pathways including cytokine-cytokine receptor interaction and T-cell-receptor signalling were upregulated in both small and large AAAs. Examples of validated genes included CTLA4 (2.01-fold upregulated in small AAA, P = 0.002), NKTR (2.37-and 2.66-fold upregulated in small and large AAA with P = 0.041 and P = 0.015, respectively), and CD8A (2.57-fold upregulated in large AAA, P = 0.004). 1,765 differentially expressed genes were identified in AOD. Pathways upregulated in AOD included metabolic and oxidative phosphorylation categories. The UCP2 gene was downregulated in AOD (3.73-fold downregulated, validated P = 0.017). In conclusion, the AAA and AOD transcriptomes were very different suggesting that AAA and AOD have distinct pathogenic mechanisms.

摘要

腹主动脉瘤(AAA)和主动脉闭塞性疾病(AOD)是老年人群发病和死亡的常见原因,以前人们认为它们有共同的病因。本研究的目的是评估人类AAA和AOD中的基因表达。我们使用从20例小AAA(≤55mm)患者、29例大AAA(>55mm)患者、9例AOD患者以及10例从器官捐献者获取的对照主动脉标本中获得的主动脉样本进行了微阵列分析。一些差异表达基因通过定量聚合酶链反应(qRT-PCR)/免疫组织化学进行了验证。我们分别在小AAA和大AAA中鉴定出840个和1014个差异表达基因。小AAA和大AAA中包括细胞因子-细胞因子受体相互作用和T细胞受体信号传导在内的免疫相关途径均上调。经验证的基因实例包括CTLA4(在小AAA中上调2.01倍,P = 0.002)、NKTR(在小AAA和大AAA中分别上调2.37倍和2.66倍,P分别为0.041和0.015)以及CD8A(在大AAA中上调2.57倍,P = 0.004)。在AOD中鉴定出1765个差异表达基因。AOD中上调的途径包括代谢和氧化磷酸化类别。UCP2基因在AOD中下调(下调3.73倍,验证后P = 0.017)。总之,AAA和AOD的转录组非常不同,表明AAA和AOD具有不同的致病机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de49/4536993/9d5be32ac08a/oncotarget-06-12984-g001.jpg

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