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- Title
869. Accelerated Re-Endothelilization in eNOS Transduced Iliac Artery Following Gene Delivery from an Adenoviral Eluting Stent.
- Authors
Sharif, Faisal; Hynes, Sean O.; Crowley, James; Daly, Kieran; O'Brien, Timothy
- Abstract
Introduction:Anti-proliferative drug eluting stents represent a useful strategy to prevent in stent restenosis. However these drugs share the liability of impairing endothelial recovery, thereby increasing the risk of stent thrombosis. Gene therapy has the potential to regenerate denuded endothelial cells following PCI. We tested the hypothesis that adenovirus encoding eNOS gene could accelerate reendothelialization when delivered from a gene eluting stent.Methods:NZW rabbits were used for the study. Balloon angioplasty of right external iliac was performed by a 2.5 × 14 mm balloon (6 ATM × 60 sec x3). Following angioplasty adenovirus coated stent (5 × 109 pfus per stent) encoding eNOS or LacZ were deployed at injury site (6 ATM × 30 sec). Gene delivery was assessed by x-gal staining for LacZ at 14 days. For re-endothelialization AdeNOS (n=4) and Adβgal (n=4) were used. Stents were retrieved at 14 days and assessed for reendothelialization with evans blue staining. eNOS expression was also assessed by immunohistochemistry.Results:Gene delivery of LacZ was demonstrated in the stented vessel at 14 days (mean 5.06%). eNOS overepression was confirmed by immunohistochemistry. 6 days post stent deployment. There was a significant acceleration of reendothelialization of stents in the eNOS treated arteries as compared to control stents. Reendothelialization was 85.34% in the eNOS treated arteries as compared to 62.66% in the Adβgal group. (p<0.005).Conclusion:Adenovirus coated stents can be used to deliver therapeutic genes to the vessel wall. eNOS gene delivery represents an alternative approach to accelerate reendothelialization following angioplasty and therefore reduce the incidence of acute stent thrombosis.Molecular Therapy (2006) 13, S334–S335; doi: 10.1016/j.ymthe.2006.08.957
- Subjects
GENE therapy; THROMBOSIS; ILIAC artery; TRANSLUMINAL angioplasty; IMMUNOHISTOCHEMISTRY
- Publication
Molecular Therapy, 2006, Vol 13, pS334
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1016/j.ymthe.2006.08.957