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

Ramanathan Kadirvel, Yong Hong Ding, Daying Dai, Debra A. Lewis, David F. Kallmes

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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 (≥ 2.4) and low (≤ 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 ≥ 1.5 and ≤ 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.

Original languageEnglish (US)
Pages (from-to)578-584
Number of pages7
JournalNeurosurgery
Volume66
Issue number3
DOIs
StatePublished - Mar 2010

Keywords

  • Aspect ratio
  • Gene expression
  • Saccular aneurysm

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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