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升主动脉瘤中基因表达谱与通路分析的整合

Integration of gene-expression profiles and pathway analysis in ascending thoracic aortic aneurysms.

作者信息

Kim Jae Hyun, Na Chan-Young, Choi Si Young, Kim Hwan Wook, Du Kim Young, Kwon Jong Bum, Chung Mee Young, Hong Jong Myeon, Park Chan Beom

机构信息

Department of Thoracic and Cardiovascular Surgery, Sejong General Hospital and Sejong Heart Institute, Bucheon, South Korea.

出版信息

Ann Vasc Surg. 2010 May;24(4):538-49. doi: 10.1016/j.avsg.2010.01.007.

DOI:10.1016/j.avsg.2010.01.007
PMID:20451796
Abstract

BACKGROUND

Despite the increasing incidence of ascending thoracic aortic aneurysms, their pathogenesis and molecular mechanisms remain unknown. The aim of this study was to identify the biological pathways of genes that are expressed differentially in ascending aortic aneurysms.

METHODS

Aneurysm wall tissues were obtained from thoracic aortic aneurysms during their repair and normal thoracic aortas from organ transplant patients. The differential expression of genes was analyzed by NimbleGen microarrays. The biological pathways and processes were identified using Kyoto Encyclopedia of Genes and Genome pathway analysis and gene ontology analysis.

RESULTS

Among 45,034 genes, 95 were differentially expressed (>two-fold change compared with control). A total of 76 genes were up-regulated and 19 genes were down-regulated in patients with ascending thoracic aneurysm. Analysis of the Kyoto Encyclopedia of Genes and Genomes pathways revealed 26 biologically functional pathways in the following categories: focal adhesion, cell junctions, peroxisome proliferator-activated receptor signaling pathway, extracellular matrix-receptor interaction, T-cell-receptor signaling pathway, B-cell-receptor signaling pathway, and regulation of the actin cytoskeleton. Differentially expressed genes were associated with 123 different gene ontology biological processes: transport, signal transduction, inflammatory response, chemotaxis, and immune response.

CONCLUSION

We identified that differentially expressed genes are associated with the pathways that are mainly involved in interactions between cells and the extracellular matrix, and with immune function. The reported data provide useful information on the molecular mechanisms underlying the formation of ascending aortic aneurysms.

摘要

背景

尽管升主动脉瘤的发病率不断上升,但其发病机制和分子机制仍不清楚。本研究的目的是确定在升主动脉瘤中差异表达的基因的生物学途径。

方法

在修复过程中从胸主动脉瘤获取瘤壁组织,并从器官移植患者获取正常胸主动脉。通过NimbleGen微阵列分析基因的差异表达。使用京都基因与基因组百科全书途径分析和基因本体分析来确定生物学途径和过程。

结果

在45,034个基因中,有95个基因差异表达(与对照组相比变化超过两倍)。在升主动脉瘤患者中,共有76个基因上调,19个基因下调。京都基因与基因组百科全书途径分析揭示了26条具有生物学功能的途径,分为以下几类:粘着斑、细胞连接、过氧化物酶体增殖物激活受体信号通路、细胞外基质-受体相互作用、T细胞受体信号通路、B细胞受体信号通路以及肌动蛋白细胞骨架的调节。差异表达的基因与123种不同的基因本体生物学过程相关:转运、信号转导、炎症反应、趋化作用和免疫反应。

结论

我们确定差异表达的基因与主要参与细胞与细胞外基质相互作用以及免疫功能的途径相关。所报道的数据为升主动脉瘤形成的分子机制提供了有用的信息。

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