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Non-viral eNOS gene delivery and transfection with stents for the treatment of restenosis

Brito, LA and Chandrasekhar, S and Little, SR and Amiji, MM (2010) Non-viral eNOS gene delivery and transfection with stents for the treatment of restenosis. BioMedical Engineering Online, 9. ISSN 1475-925X

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Background: In this study, we have examined local non-viral gene delivery, transfection, and therapeutic efficacy of endothelial nitric oxide synthase (eNOS) encoding plasmid DNA administered using coated stents in a rabbit iliac artery restenosis model.Methods: Lipopolyplexes (LPPs) with eNOS expressing plasmid DNA were immobilized on stainless steel stents using poly(D,L-lactide-co-glycolide) (PLGA) and type B gelatin coatings. The gene-eluting stents were implanted bilaterally in the denuded iliac arteries and eNOS transfection and therapeutic efficacy were examined 14 days after implantation.Results: The results show that non-viral lipopolyplex-coated stents can efficiently tranfect eNOS locally in the arterial lumen assessed by PCR and ELISA. Human eNOS ELISA levels were significantly raised 24 hours after transfection compared to controls (125 pg eNOS compared to <50 pg for all controls including naked DNA). Local eNOS production suppressed smooth muscle cell proliferation and promoted re-endothelialization of the artery showing a significant reduction in restenosis of 1.75 neointima/media ratio for stents with lipoplexes encoding eNOS compared with 2.3 neointima/media ratio for stents with lipoplexes encosing an empty vector.Conclusions: These results support the hypothesis that a potent non-viral gene vector encoding for eNOS coated onto a stent can inhibit restenosis through inhibition of smooth muscle cell growth and promotion of a healthy endothelium. © 2010 Brito et al; licensee BioMed Central Ltd.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Brito, LA
Chandrasekhar, S
Little, SRsrlittle@pitt.eduSRLITTLE0000-0002-7000-3931
Amiji, MM
Date: 27 September 2010
Date Type: Publication
Journal or Publication Title: BioMedical Engineering Online
Volume: 9
DOI or Unique Handle: 10.1186/1475-925x-9-56
Schools and Programs: Swanson School of Engineering > Chemical Engineering
Refereed: Yes
ISSN: 1475-925X
Date Deposited: 14 Nov 2016 20:21
Last Modified: 02 Feb 2019 15:55


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