Introduction
The biological mechanisms leading to aneurysm healing or rare complications such as delayed aneurysm ruptures after flow-diverter placement remain poorly understood. We used RNA-sequencing (RNA-seq) following implantation of coils or flow-diverters in elastase aneurysms in rabbits to identify genes and pathways of potential interest.
Methods
Aneurysms were treated with coils (n=5) or flow-diverters (n=4) or left untreated for controls (n=6). Messenger RNA were isolated from the aneurysms at 4 weeks following treatment. RNA samples were processed using RNA-seq technology and analyzed using the Ingenuity Pathway Analysis tool.
Results
Using RNA-seq for coiled versus untreated aneurysms, 464/9990 genes (4.6%) were differentially expressed (58 down-regulated, 406 up-regulated). Comparing flow-diverter versus untreated aneurysms, 177/10041 (1.8%) genes were differentially expressed (8 down-regulated, 169 up-regulated). Comparing 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 (Dectin1 and HHIP) 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 different 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 recurrence of coiled aneurysms.