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

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, and Golledge, Jonathan (2015) Differential gene expression in human abdominal aortic aneurysm and aortic occlusive disease. Oncotarget, 6 (15). pp. 1-13.

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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.

Item ID: 38903
Item Type: Article (Scholarly Work)
Keywords: aortic aneurysm, abdominal, arterial occlusive diseases, tissue array analysis
ISSN: 1949-2553
Funders: Queensland Government, National Health and Medical Research Council of Australia (NHMRC), Townsville Hospital Private Practice Trust, National Heart Foundation of Australia (NHF), Technical University of Dresden, W. L. Gore and Associates, Vascutek Deutschland
Projects and Grants: NHMRC grant 1020955, NHMRC grant 1021416, NHMRC grant 1063476, NHMRC grant 1000967, NHMRC Practitioner Fellowship 1019921, NHF G09B4339
Date Deposited: 19 Nov 2015 02:27
FoR Codes: 06 BIOLOGICAL SCIENCES > 0604 Genetics > 060405 Gene Expression (incl Microarray and other genome-wide approaches) @ 80%
11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl Cardiovascular Diseases) @ 20%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 100%
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