Differential gene expression in well-healed and poorly healed experimental aneurysms after coil treatment.
OBJECTIVE
To compare gene expression patterns between well-healed and poorly healed aneurysms following coil embolization in a rabbit model.


METHODS
The Institutional Animal Care and Use Committee approved all procedures before initiation of the study. Elastase-induced, saccular aneurysms were created in rabbits and embolized by using platinum microcoils. Group 1 aneurysms were densely packed (volumetric packing density, >30%) to achieve good healing, whereas group 2 aneurysms were loosely packed (volumetric packing density, <20%), which yields poor healing. At 2 or 4 weeks after implantation, samples were harvested. RNA was isolated separately from the necks and domes of the aneurysms and analyzed by using a microarray containing 294 rabbit genes. Genes with significant differences between groups (P < .05; false discovery rate, <0.1; fold change, ≥1.2 and ≤0.8) were considered differentially expressed.


RESULTS
At 2 weeks, of 294 genes, 22 (7.5%) genes in the neck and 14 (4.8%) genes in the dome were differentially expressed between groups; at 4 weeks, of 294 genes, 25 (8.5%) genes in the neck and 17 (5.8%) genes in the dome were differentially expressed between groups. Genes overexpressed in group 1 as compared with group 2 aneurysms included those encoding proteases, adhesion molecules, and chemoattractant molecules. Conversely, group 2 aneurysms had increased expression of genes encoding structural molecules, including collagens, as compared with expression in group 1 aneurysms.


CONCLUSIONS
Robust healing after coil embolization is associated with substantial biological activity, as evidenced by overexpression of proteases, adhesion molecules, and chemoattractants. However, contrary to prior hypotheses, structural molecules such as collagen were not associated with the healing response in the rabbit model.
Kadirvel
Ramanathan
R
Department of Radiology, Neuroradiology Research Laboratory, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
Ding
Yong-Hong
YH
Dai
Daying
D
Lewis
Debra A
DA
Kallmes
David F
DF
D000792:Angiography; D000818:Animals; D003094:Collagen / Q000235:genetics; D004621:Embolization, Therapeutic; D005260:Female; D015870:Gene Expression; D007150:Immunohistochemistry; D002532:Intracranial Aneurysm / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D020411:Oligonucleotide Array Sequence Analysis; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014945:Wound Healing / Q000502:physiology*
D003094:Collagen