Email updates

Keep up to date with the latest news and content from BMC Genomics and BioMed Central.

Open Access Research article

Whole genome expression profiling reveals a significant role for immune function in human abdominal aortic aneurysms

Guy M Lenk1, Gerard Tromp12, Shantel Weinsheimer1, Zoran Gatalica4, Ramon Berguer5 and Helena Kuivaniemi13*

Author Affiliations

1 Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA

2 Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA

3 Department of Surgery, Wayne State University School of Medicine, Detroit, MI, USA

4 Department of Pathology, Creighton University School of Medicine, Omaha, NE, USA

5 Department of Surgery, University of Michigan, Ann Arbor, MI, USA

For all author emails, please log on.

BMC Genomics 2007, 8:237  doi:10.1186/1471-2164-8-237

Published: 16 July 2007

Abstract

Background

Abdominal aortic aneurysms are a common disorder with an incompletely understood etiology. We used Illumina and Affymetrix microarray platforms to generate global gene expression profiles for both aneurysmal (AAA) and non-aneurysmal abdominal aorta, and identified genes that were significantly differentially expressed between cases and controls.

Results

Affymetrix and Illumina arrays included 18,057 genes in common; 11,542 (64%) of these genes were considered to be expressed in either aneurysmal or normal abdominal aorta. There were 3,274 differentially expressed genes with a false discovery rate (FDR) ≤ 0.05. Many of these genes were not previously known to be involved in AAA, including SOST and RUNX3, which were confirmed using Q-RT-PCR (Pearson correlation coefficient for microarray and Q-RT-PCR data = 0.89; p-values for differences in expression between AAA and controls for SOST: 4.87 × 10-4 and for RUNX3: 4.33 × 10-5). Analysis of biological pathways, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), indicated extreme overrepresentation of immune related categories. The enriched categories included the GO category Immune Response (GO:0006955; FDR = 2.1 × 10-14), and the KEGG pathways natural killer cell mediated cytotoxicity (hsa04650; FDR = 5.9 × 10-6) and leukocyte transendothelial migration (hsa04670; FDR = 1.1 × 10-5).

Conclusion

Previous studies have provided evidence for the involvement of the immune system in AAA. The current expression analysis extends these findings by demonstrating broad coordinate gene expression in immunological pathways. A large number of genes involved in immune function were differentially expressed in AAA, and the pathway analysis gave these results a biological context. The data provide valuable insight for future studies to dissect the pathogenesis of human AAA. These pathways might also be used as targets for the development of therapeutic agents for AAA.