Whole genome expression profiling reveals a significant role for immune function in human abdominal aortic aneurysms.
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 x 10-4 and for RUNX3: 4.33 x 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 x 10-14), and the KEGG pathways natural killer cell mediated cytotoxicity (hsa04650; FDR = 5.9 x 10-6) and leukocyte transendothelial migration (hsa04670; FDR = 1.1 x 10-5).


CONCLUSIONS
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.
Lenk
Guy M
GM
Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA. glenk@med.wayne.edu <glenk@med.wayne.edu>
Tromp
Gerard
G
Weinsheimer
Shantel
S
Gatalica
Zoran
Z
Berguer
Ramon
R
Kuivaniemi
Helena
H
D017544:Aortic Aneurysm, Abdominal / Q000235:genetics* / Q000276:immunology; D002465:Cell Movement; D030541:Databases, Genetic; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005821:Genetic Techniques; D016678:Genome; D015894:Genome, Human; D006801:Humans; D007107:Immune System; D008954:Models, Biological; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction