Oncotarget

Research Papers: Pathology:

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

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

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Oncotarget. 2015; 6:12984-12996. https://doi.org/10.18632/oncotarget.3848

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Abstract

Erik Biros1,*, Gabor Gäbel2,*, Corey S. Moran1, Charlotte Schreurs3, Jan H. N. Lindeman3, Philip J. Walker4, Maria Nataatmadja5, Malcolm West5, Lesca M. Holdt6, Irene Hinterseher7, Christian Pilarsky8 and Jonathan Golledge1,9

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

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

3 Department of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands

4 Royal Brisbane Clinical School, The University of Queensland, Queensland, Australia

5 The Cardiovascular Research Group, Department of Medicine, The University of Queensland, Queensland, Australia

6 Institute of Laboratory Medicine, Ludwig Maximilians University Munich, Munich, Germany

7 Department of General, Visceral, Vascular and Thoracic Surgery, Charité Universitätsmedizin Berlin, Charité Campus Mitte, Berlin, Germany

8 Department of Vascular, Thoracic and Visceral Surgery, TU-Dresden, Dresden, Germany

9 Department of Vascular and Endovascular Surgery, The Townsville Hospital, Townsville, Queensland, Australia

* These authors have contributed equally to this work

Correspondence to:

Jonathan Golledge, email:

Keywords: aortic aneurysm, abdominal, arterial occlusive diseases, tissue array analysis

Received: March 02, 2015 Accepted: March 21, 2015 Published: April 15, 2015

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.


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