Differential gene expression in the proximal neck of human abdominal aortic aneurysm

Biros, Erik, Moran, Corey S., Rush, Catherine M., Gäbel, Gabor, Schreurs, Charlotte, Lindeman, Jan H.N., Walker, Philip J., Nataatmadja, Maria, West, Malcolm, Holdt, Lesca M., Hinterseher, Irene, Pilarsky, Christian, and Golledge, Jonathan (2014) Differential gene expression in the proximal neck of human abdominal aortic aneurysm. Atherosclerosis, 233 (1). pp. 211-218.

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Abstract

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.

Item ID: 33007
Item Type: Article (Research - C1)
ISSN: 1879-1484
Keywords: aortic aneurysm, abdominal, tissue array analysis, B-lymphocytes, inflammation
Funders: Queensland Government, National Health and Medical Research Council (NHMRC), Townsville Hospital Private Practice Trust Fund, National Heart Foundation of Australia (NHF)
Projects and Grants: NHF G09B4339
Date Deposited: 30 Apr 2014 09:59
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl Cardiovascular Diseases) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 100%
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