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.


CONCLUSIONS
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.
Kadirvel
Ramanathan
R
Neuroradiology Research Laboratory, Department of Radiology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Ding
Yong-Hong
YH
Dai
Daying
D
Lewis
Debra A
DA
Kallmes
David F
DF
D000783:Aneurysm / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010196:Pancreatic Elastase / Q000009:adverse effects*; D011817:Rabbits
D010196:Pancreatic Elastase