TY - JOUR
T1 - Differential expression of genes in elastase-induced saccular aneurysms with high and low aspect ratios
AU - Kadirvel, Ramanathan
AU - Ding, Yong Hong
AU - Dai, Daying
AU - Lewis, Debra A.
AU - Kallmes, David F.
PY - 2010/3
Y1 - 2010/3
N2 - 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.
AB - 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.
KW - Aspect ratio
KW - Gene expression
KW - Saccular aneurysm
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U2 - 10.1227/01.NEU.0000365769.78334.8C
DO - 10.1227/01.NEU.0000365769.78334.8C
M3 - Article
C2 - 20173552
AN - SCOPUS:77649141287
SN - 0148-396X
VL - 66
SP - 578
EP - 584
JO - Neurosurgery
JF - Neurosurgery
IS - 3
ER -