Differential Expression of Genes in Elastase-Induced Saccular Aneurysms With High and Low Aspect Ratios

Abstract

Morphologic features are thought to play a critical role in the rupture of intracranial, saccular aneurysms. The objective of this study was to investigate the gene expression pattern of saccular aneurysms with distinct morphologic patterns. 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. 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. 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.