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

Abstract

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.

Figure 1

Schematic of tissue chosen for mRNA expression studies: 2 and 3 mm axial sections of aneurysm tissue, from the neck and fundus, respectively, were harvested.

Figure 2

Angiographic progression of stented lateral wall aneurysms with time. A,C) represent initial images at 4-6 weeks following surgical creation. B,D) show improved angiographic appearance following stenting, but not complete obliteration, at 4 days and 12 weeks respectively.

Figure 3

Photographs of stented (A-D) and non-stented (E-F) control aneurysms. Good neointima formation in (A, B), filling aneurysm body and neck and incorporating stent struts. C, D) reveal incomplete neointimal filling, with the aneurismal defect evident on en-face as well as sagittal views. E, F) demonstration the widely patent ostia and minimal neointimal filling typical of non-stented control aneurysms.

Figure 4

Gene expression associated with stenting. Results of RT-PCR analyses, expressed as specimen/arterial controls ratio, according to time. A) Gene expression at the fundus B) Gene expression at the neck of aneurysms. = Stented = Not stented).

Figure 4

Gene expression associated with stenting. Results of RT-PCR analyses, expressed as specimen/arterial controls ratio, according to time. A) Gene expression at the fundus B) Gene expression at the neck of aneurysms. = Stented = Not stented).