ABSTRACT
SUMMARY: Recanalization after coil occlusion is a concern for long-term results of endovascular treatment. Knowledge of molecular events following coil occlusion and recanalization could help design specific strategies to promote permanent occlusion. Platinum coils were implanted into canine maxillary, vertebral or lingual arteries. Coil occlusion (treatment 1), routinely followed by recanalization was compared with two strategies to prevent recanalization: beta radiation using (32)P coils (treatment 2) and endothelial denudation, using an endovascular device, followed by coil occlusion (treatment 3). The evolution of initial complete occlusions was followed by angiography and pathology at three months. Levels of messenger RNA of vWF (von Willebrand factor), SMA (smooth muscle actin), CD14, CD31 (or PECAM-1: Platelet Endothelial Cell Adhesion Molecule-1), PDGFBB (platelet-derived growth factor), TGF-b1 (transforming growth factor), MCP-1 (macrophage chemoattractant protein), Angiopoietins, Metalloproteinases-9, 14 and inhibitors (TIMP- 2, 4) were followed by Reverse Transcription and Polymerase Chain Reaction (RT-PCR). Analyses were performed one, four, seven and 14 days after coiling, and levels of expression after the three treatments were compared using ANOVAs. Intact arteries treated with platinum coils routinely recanalize (100%), but arteries treated by denudation and coiling or with radioactive coils recanalize in only 17% and 4% respectively (P<.001). Recanalization was associated with increased levels of vWF mRNA at seven days, a finding that was not observed with denudation or radiation (P=.015). There was no other significant difference. Recanalization is associated with early vWF expression, perhaps reflecting the development of endothelialized channels through thrombus formed after coil occlusion.
ABSTRACT
SUMMARY: Intracranial stents are increasingly used in the endovascular treatment of aneurysms, but very little is known regarding their effect on the cellular and molecular evolution of aneurysms. Bilateral venous pouch lateral wall carotid aneurysms were created in 20 dogs. All dogs then underwent angiography and balloon-expandable stenting of one aneurysm four to six weeks later. Fifteen dogs underwent aneurysm harvesting at one day (n=3), four days (n=4), seven days (n=3), and 14 days (n=5) for mRNA expression analysis, using axial sections taken from the aneurysm neck and fundus for RTPCR amplification of four cytokines or growth factors: TNF-a, TGF-b1, MCP-1, and PDGFBB; two adhesion molecules: VCAM-1 and PECAM-1; five matrix modifying agents; MMP- 2, 9, TIMPs 1, 3, 4, and two cellular markers: CD34 and a-SMA. Five other dogs, sacrificed at 12 weeks, were examined for extent of filling of the aneurysm neck with organized tissue and for neointima formation at the aneurysm ostium. Angiography was performed prior to sacrifice in all animals, and compared with initial studies. Eleven out of 20 stented aneurysms showed a favorable angiographic evolution, while none of the 20 nonstented aneurysms improved (p=0.001). Pathology showed partially occluded aneurysms, with neointima formation around the stent struts.Observed trends in mRNA expression, that stenting increased expression of genes involved in organization and neointima formation, agreed with experimental hypotheses, but differences between stented and non-stented aneurysms did not reach statistical significance. Parent vessel stenting was associated with angiographic improvement of aneurysm appearance. Modifications in mRNA expression patterns following stenting deserve further study to better establish potential molecular targets to promote aneurysm healing.
