Differential expression of genes in elastase-induced saccular aneurysms with high and low aspect ratios.

BACKGROUND

Morphologic features are thought to play a critical role in the rupture of intracranial, saccular aneurysms.

OBJECTIVE

The objective of this study was to investigate the gene expression pattern of saccular aneurysms with distinct morphologic patterns.

METHODS

Elastase-induced saccular aneurysms with high (>or= 2.4) and low (<or= 1.6) aspect ratios (ARs) (height to neck width) were created in 15 rabbits (n = 9 for high AR and n = 6 for low AR). RNA was isolated from the aneurysms and analyzed using a microarray containing 294 rabbit genes of interest. Genes with a statistically significant difference between low and high AR (P < .05) and a fold change of >or= 1.5 and <or= 0.75 to represent up- and down-regulation in high AR compared with low AR were used to identify pathways for further investigation.

RESULTS

Fourteen genes (4.8%) were differentially expressed in high-AR aneurysms compared with low-AR aneurysms. The expression of osteopontin, tissue inhibitor of matrix metalloproteinase, haptoglobin, cathepsin L, collagen VIII, fibronectin, galectin 3, secreted frizzled-related protein 2, CD14, decorin, and annexin I were up-regulated, whereas the expression of myosin light chain kinase, Fas antigen, and CD34 were down-regulated in high-AR aneurysms.

CONCLUSION

In a rabbit model of saccular aneurysm, high AR was associated with differential expression of inflammatory/immunomodulatory genes, structural genes, genes related to proteolytic enzymes and extracellular matrix-related genes. These findings may focus efforts on targets aimed at avoiding spontaneous rupture of intracranial, saccular aneurysms.