Integration of gene-expression profiles and pathway analysis in ascending thoracic aortic aneurysms.

BACKGROUND

Despite the increasing incidence of ascending thoracic aortic aneurysms, their pathogenesis and molecular mechanisms remain unknown. The aim of this study was to identify the biological pathways of genes that are expressed differentially in ascending aortic aneurysms.

METHODS

Aneurysm wall tissues were obtained from thoracic aortic aneurysms during their repair and normal thoracic aortas from organ transplant patients. The differential expression of genes was analyzed by NimbleGen microarrays. The biological pathways and processes were identified using Kyoto Encyclopedia of Genes and Genome pathway analysis and gene ontology analysis.

RESULTS

Among 45,034 genes, 95 were differentially expressed (>two-fold change compared with control). A total of 76 genes were up-regulated and 19 genes were down-regulated in patients with ascending thoracic aneurysm. Analysis of the Kyoto Encyclopedia of Genes and Genomes pathways revealed 26 biologically functional pathways in the following categories: focal adhesion, cell junctions, peroxisome proliferator-activated receptor signaling pathway, extracellular matrix-receptor interaction, T-cell-receptor signaling pathway, B-cell-receptor signaling pathway, and regulation of the actin cytoskeleton. Differentially expressed genes were associated with 123 different gene ontology biological processes: transport, signal transduction, inflammatory response, chemotaxis, and immune response.

CONCLUSION

We identified that differentially expressed genes are associated with the pathways that are mainly involved in interactions between cells and the extracellular matrix, and with immune function. The reported data provide useful information on the molecular mechanisms underlying the formation of ascending aortic aneurysms.