Purpose
Intracranial, saccular aneurysms are associated with chronic remodeling of the arterial wall. The pathobiology of aneurysm growth and rupture is poorly understood. The objective of the present study was to study the gene expression patterns in elastase-induced saccular aneurysms in rabbits five years after aneurysm creation as compared to control, unoperated arteries.
Materials and Methods
Elastase-induced saccular aneurysms were created in 25 rabbits and followed up to five years. Thirteen rabbits died during follow-up for reasons unrelated to the aneurysms. RNA was isolated from aneurysm tissue and the control contralateral common carotid artery in 5 of the 12 surviving subjects and analyzed for gene expression using human gene microarrays. Genes with statistical differences between groups (p<0.05 and fold change ≥1.5 and ≤0.75) were considered differentially expressed. RT-PCR was used for confirmation of gene microarray findings for selected genes.
Results
Fifty (0.33%) of 13,353 genes were differentially expressed in the aneurysms compared with the unoperated control arteries. Molecular and functional pathway analysis revealed that immunoregulatory molecules, growth factors, cell adhesion molecules, and structural molecules were differentially expressed in the aneurysms as compared to controls. RT-PCR results of selected genes confirmed the differential expression identified using the gene chip microarray.
Conclusions
Significant modulation in a variety of biochemical and cellular functions in chronic aneurysms provides molecular insights into the pathophysiology of saccular aneurysms.