TY - JOUR T1 - Differential Gene Expression in Coiled versus Flow-Diverter-Treated Aneurysms: RNA Sequencing Analysis in a Rabbit Aneurysm Model JF - American Journal of Neuroradiology JO - Am. J. Neuroradiol. SP - 1114 LP - 1121 DO - 10.3174/ajnr.A4648 VL - 37 IS - 6 AU - A. Rouchaud AU - C. Johnson AU - E. Thielen AU - D. Schroeder AU - Y.-H. Ding AU - D. Dai AU - W. Brinjikji AU - J. Cebral AU - D.F. Kallmes AU - R. Kadirvel Y1 - 2016/06/01 UR - http://www.ajnr.org/content/37/6/1114.abstract N2 - BACKGROUND AND PURPOSE: The biologic mechanisms leading to aneurysm healing or rare complications such as delayed aneurysm ruptures after flow-diverter placement remain poorly understood. We used RNA sequencing following implantation of coils or flow diverters in elastase aneurysms in rabbits to identify genes and pathways of potential interest.MATERIALS AND METHODS: Aneurysms were treated with coils (n = 5) or flow diverters (n = 4) or were left untreated for controls (n = 6). Messenger RNA was isolated from the aneurysms at 4 weeks following treatment. RNA samples were processed by using RNA-sequencing technology and were analyzed by using the Ingenuity Pathway Analysis tool.RESULTS: With RNA sequencing for coiled versus untreated aneurysms, 464/9990 genes (4.6%) were differentially expressed (58 down-regulated, 406 up-regulated). When we compared flow-diverter versus untreated aneurysms, 177/10,041 (1.8%) genes were differentially expressed (8 down-regulated, 169 up-regulated). When we compared flow-diverter versus coiled aneurysms, 13/9982 (0.13%) genes were differentially expressed (8 down-regulated, 5 up-regulated). Keratin 8 was overexpressed in flow diverters versus coils. This molecule may potentially play a critical role in delayed ruptures due to plasmin production. We identified overregulation of apelin in flow diverters, supporting the preponderance of endothelialization, whereas we found overexpression of molecules implicated in wound healing (dectin 1 and hedgehog interacting protein) for coiled aneurysms. Furthermore, we identified metallopeptidases 1, 12, and 13 as overexpressed in coiled versus untreated aneurysms.CONCLUSIONS: We observed different physiopathologic responses after endovascular treatment with various devices. Flow diverters promote endothelialization but express molecules that could potentially explain the rare delayed ruptures. Coils promote wound healing and express genes potentially implicated in the recurrence of coiled aneurysms.DAPL1death associated protein-like 1FGFBP1fibroblast growth factor binding protein 1HHIPhedgehog-interacting proteinIAintracranial aneurysmIL6interleukin 6IPAIngenuity Pathway AnalysisMMPmatrix metalloproteinasemRNAmessenger RNAPRNDprion protein 2RNA-seqRNA sequencingSRCIN1SRC kinase signaling inhibitor 1 ER -