Effects of stenting the parent artery on aneurysm filling and gene expression of various potential factors involved in healing of experimental aneurysms

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 RT-PCR amplification of four cytokines or growth factors: TNF-a, TGF-b(1), MCP-1, and PDGF-BB; 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 non-stented 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.