Gene expression profiling of experimental saccular aneurysms using deoxyribonucleic acid microarrays

BACKGROUND AND PURPOSE: The molecular characteristics of the pathophysiology of saccular aneurysms remain poorly understood. The purpose of the current study was to investigate the expression of various groups of genes at different stages of aneurysm age in elastase-induced saccular aneurysms in rabbits through the use of deoxyribonucleic acid (DNA) microarrays. MATERIALS AND METHODS: A microarray consisting of genes related to cell adhesion, apoptosis, cell signaling, growth, inflammation, vascular remodeling, and oxidative stress was constructed by using rabbit nucleotide sequences. Elastase-induced saccular aneurysms were created at the origin of the right common carotid artery (CCA) in 12 rabbits. Two weeks (n = 6) and 12 weeks (n = 6) after aneurysm creation, ribonucleic acid (RNA) was isolated from the aneurysm and the control unoperated left CCA and was used for microarray experiments. Real-time polymerase chain reaction (RT-PCR) was performed for validation of microarray results. RESULTS: Of 209 genes, 157 (75%) at 2 weeks and 88 (42%) at 12 weeks demonstrated statistically significant differential expression between aneurysm tissue and the control left CCA tissue (P <.05). Multiple genes implicated in vessel wall remodeling were found to be elevated at 2 weeks and at 12 weeks. Expression of cell adhesion molecules and antioxidant enzymes was down-regulated at 2 weeks but was not significantly different from that of controls at 12 weeks. Most transcription factors, inflammatory genes, and structural genes showed underexpression at both time points. The expression profiles of selected genes were confirmed by RT-PCR. CONCLUSION: Multiple genes in diverse pathways have been differentially expressed in the rabbit aneurysm model.