Gene-eluting stents: non-viral, liposome-based gene delivery of eNOS to the blood vessel wall in vivo results in enhanced endothelialization but does not reduce restenosis in a hypercholesterolemic model

DC FieldValueLanguage
dc.contributor.authorSharif, F.en
dc.contributor.authorHynes, Sean O.en
dc.contributor.authorMcCullagh, K. J. A.en
dc.contributor.authoret al.en
dc.date.accessioned2013-11-29T09:52:31Z-
dc.date.available2013-11-29T09:52:31Z-
dc.date.copyright2011 Nature Publishing Groupen
dc.date.issued2011-06-30en
dc.identifier.citationGene Therapyen
dc.identifier.urihttp://hdl.handle.net/10197/5054-
dc.description.abstractAlthough successful, drug-eluting stents require significant periods of dual anti-platelet therapy with a persistent risk of late stent thrombosis due to inhibition of re-endothelialization. Endothelial regeneration is desirable to protect against in-stent thrombosis. Gene-eluting stents may be an alternative allowing inhibition of neointima and regenerating endothelium. We have shown that adenoviral endothelial nitric oxide synthase (eNOS) delivery can result in significantly decreased neointimal formation and enhanced re-endothelialization. Here, we examined non-viral reporter and therapeutic gene delivery from a stent. We coated lipoplexes directly onto the surface of stents. These lipostents were then deployed in the injured external iliac artery of either normal or hypercholesterolemic New Zealand White rabbits and recovered after 28 days. Lipoplexes composed of lipofectin and a reporter lacZ gene or therapeutic eNOS gene were used. We demonstrated efficient gene delivery at 28 days post-deployment in the media (21.3±7.5%) and neointima (26.8±11.2%). Liposomal delivery resulted in expression in macrophages between the stent struts. This resulted in improved re-endothelialization as detected by two independent measures compared with vector and stent controls (P<0.05 for both). However, in contrast to viral delivery of eNOS, liposomal eNOS does not reduce restenosis rates. The differing cell populations targeted by lipoplexes compared with adenoviral vectors may explain their ability to enhance re-endothelialization without affecting restenosis. Liposome-mediated gene delivery can result in prolonged and localized transgene expression in the blood vessel wall in vivo. Furthermore, lipoeNOS delivery to the blood vessel wall results in accelerated re-endothelialization; however, it does not reduce neointimal formation.en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.subjectendothelializationen
dc.subjectcoronary artery stentsen
dc.subjectrestenosisen
dc.subjectlate stent thrombosisen
dc.subjectliposomeen
dc.titleGene-eluting stents: non-viral, liposome-based gene delivery of eNOS to the blood vessel wall in vivo results in enhanced endothelialization but does not reduce restenosis in a hypercholesterolemic modelen
dc.typeJournal Articleen
dc.internal.availabilityFull text availableen
dc.statusPeer revieweden
dc.identifier.volume19en
dc.identifier.issue3en
dc.identifier.startpage321en
dc.identifier.endpage328en
dc.identifier.doi10.1038/gt.2011.92-
dc.neeo.contributorSharif|F.|aut|-
dc.neeo.contributorHynes|Sean O.|aut|-
dc.neeo.contributorMcCullagh|K. J. A.|aut|-
dc.neeo.contributoret al.||aut|-
dc.internal.notesPaper33.pdfen
dc.description.othersponsorshipEnterprise Ireland Grant (CFTD 105-07). TOB is also funded by a CSET Grant to REMEDI from Science Foundation Irelanden
dc.description.adminDeposited by bulk importen
dc.date.updated2013-11-27T16:35:50.274Zen
item.grantfulltextopen-
item.fulltextWith Fulltext-
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