Abstract WMP27: Differential Gene Expression in Coiled Versus Flow-diverter Treated Aneurysms: a RNA-Seq Analysis in Rabbit Aneurysm Model

Abstract

Introduction: Numerous endovascular tools exist for the treatment of intracranial aneurysms with an increased use of flow-diverting devices in recent years. However, the biological mechanisms leading to aneurysm healing or potential complications such as delayed aneurysm ruptures after flow-diverter treatment are not yet well established. We used RNA-sequencing technology to identify genes relevant for biological impact of coils and flow-diverters in elastase-induced saccular aneurysms in rabbits and to identify genes and pathways of potential clinical interest. Methods: Elastase-induced saccular aneurysms were created at the origin of the right common carotid artery. Aneurysms were treated with coils (n=5) or flow-diverters (Pipeline Embolic Device, Covidien, CA) (n=4). Untreated aneurysms (n=6) were used as controls. Messenger RNA and microRNA were isolated from the aneurysms at 4 weeks following treatment. RNA samples were processed using RNA-seq technology. RNA-seq results were analyzed by using the Ingenuity Pathway Analysis tool. Results: Using RNA sequencing for coiled versus non-treated aneurysms, 464 genes were found to be differentially expressed with 58 genes down regulated and 406 genes up regulated. Using the same criteria for the flow-diverter treated aneurysms, 177 genes were found to be differentially expressed with 8 genes down regulated and 169 genes up regulated. Comparing coiled versus flow-diverter treated aneurysms, 13 genes were significantly differentially expressed with 8 down regulated and 5 up regulated genes. Genes identified with the highest interest for aneurysms healing were fibroblast growth factor-23, matrix metalloproteinases (MMP)-1, Scinderin and Basigin (implicated in MMP-2 and MMP-9 regulation). Pathway analysis associated these genes with inflammatory response, cellular migration, and coagulation, among other functions. Conclusions: RNA-sequencing analysis of rabbit aneurysms revealed differential regulation of some key pathways, including inflammation and cellular migration that could explain the different biological mechanisms implicated in aneurysms healing either after coiling or flow-diverter treatments and could explain potential device-related complications.