title: Differential Gene Expression in Coiled versus Flow-Diverter-Treated Aneurysms: RNA Sequencing Analysis in a Rabbit Aneurysm Model.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: From the Applied Neuroradiology Laboratory (A.R., C.J., E.T., D.S., Y.-H.D., D.D., W.B., D.F.K., R.K.) Rouchaud.Aymeric@mayo.edu aymeric.rouchaud@gmail.com.
authors.forename: A
authors.identifier: 0000-0003-0902-3375
authors.initials: A
authors.lastname: Rouchaud
authors.affiliation: From the Applied Neuroradiology Laboratory (A.R., C.J., E.T., D.S., Y.-H.D., D.D., W.B., D.F.K., R.K.).
authors.forename: C
authors.identifier: 0000-0001-7344-5332
authors.initials: C
authors.lastname: Johnson
authors.affiliation: From the Applied Neuroradiology Laboratory (A.R., C.J., E.T., D.S., Y.-H.D., D.D., W.B., D.F.K., R.K.).
authors.forename: E
authors.identifier: 0000-0002-4453-0244
authors.initials: E
authors.lastname: Thielen
authors.affiliation: From the Applied Neuroradiology Laboratory (A.R., C.J., E.T., D.S., Y.-H.D., D.D., W.B., D.F.K., R.K.).
authors.forename: D
authors.identifier: 0000-0002-9676-232X
authors.initials: D
authors.lastname: Schroeder
authors.affiliation: From the Applied Neuroradiology Laboratory (A.R., C.J., E.T., D.S., Y.-H.D., D.D., W.B., D.F.K., R.K.).
authors.forename: Y-H
authors.identifier: 0000-0003-4329-3192
authors.initials: YH
authors.lastname: Ding
authors.affiliation: From the Applied Neuroradiology Laboratory (A.R., C.J., E.T., D.S., Y.-H.D., D.D., W.B., D.F.K., R.K.).
authors.forename: D
authors.identifier: 0000-0003-4051-6450
authors.initials: D
authors.lastname: Dai
authors.affiliation: From the Applied Neuroradiology Laboratory (A.R., C.J., E.T., D.S., Y.-H.D., D.D., W.B., D.F.K., R.K.) Department of Radiology (W.B., D.F.K.), Mayo Clinic, Rochester, Minnesota.
authors.forename: W
authors.identifier: 0000-0001-5271-5524
authors.initials: W
authors.lastname: Brinjikji
authors.affiliation: Department of Bioengineering (J.C.), George Mason University, Fairfax, Virginia.
authors.forename: J
authors.identifier: 0000-0002-3216-0856
authors.initials: J
authors.lastname: Cebral
authors.affiliation: From the Applied Neuroradiology Laboratory (A.R., C.J., E.T., D.S., Y.-H.D., D.D., W.B., D.F.K., R.K.) Department of Radiology (W.B., D.F.K.), Mayo Clinic, Rochester, Minnesota.
authors.forename: D F
authors.identifier: 0000-0002-8495-0040
authors.initials: DF
authors.lastname: Kallmes
authors.affiliation: From the Applied Neuroradiology Laboratory (A.R., C.J., E.T., D.S., Y.-H.D., D.D., W.B., D.F.K., R.K.).
authors.forename: R
authors.identifier: 0000-0002-6786-9953
authors.initials: R
authors.lastname: Kadirvel
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D057510:Endovascular Procedures / Q000295:instrumentation*; D015870:Gene Expression; D002532:Intracranial Aneurysm / Q000601:surgery*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis*; D011817:Rabbits; D014945:Wound Healing / Q000502:physiology
chemical_list: D012333:RNA, Messenger