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Article: Prevention of chronic deterioration of heart allograft by recombinant adeno-associated virus-mediated heme oxygenase-1 gene transfer

TitlePrevention of chronic deterioration of heart allograft by recombinant adeno-associated virus-mediated heme oxygenase-1 gene transfer
Authors
KeywordsArteriosclerosis
Gene therapy
Grafting
Remodeling
Transplantation
Issue Date2003
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://circ.ahajournals.org
Citation
Circulation, 2003, v. 107 n. 20, p. 2623-2629 How to Cite?
AbstractBackground - Allograft deterioration is the major obstacle to organ transplantation as a long-term treatment of end-stage heart failure. In this study, we transduced the antioxidant gene, heme oxygenase-1 (HO-1), to heart grafts using a recombinant adeno-associated viral vector (rAAV) in a rat heart transplantation model and investigated its potentiality in prevention of chronic graft deterioration. Methods and Results - rAAV/HO-1 was administered to heart grafts through the coronary arteries during cold preservation. We investigated the expression patterns and activities of transgene, graft survival, graft histomorphology, and relevance of HO-1 expression on graft survival and chronic graft deterioration by itself. Long-term allograft survival can be achieved by rAAV/HO-1-mediated stable transgene expression. The development of graft arteriosclerosis and interstitial fibrosis was prevented in rAAV/HO-1-transduced allografts on day 100. rAAV/HO-1-mediated long-term graft protection was accompanied by remarkable downregulation of the intragraft mRNA level of macrophage migration inhibitory factor, tumor necrosis factor-α, and transforming growth factor-β1. Blockage of HO activities by zinc protoporphyrin IX at different posttransplant phases showed that the stable expression of HO-1 is a prerequisite for both survival of grafts and prevention of graft arteriosclerosis. Conclusions - rAAV/HO-1 gene transfer represents a novel therapeutic approach to prevent chronic allograft deterioration in clinical heart transplantation.
Persistent Identifierhttp://hdl.handle.net/10722/84520
ISSN
2015 Impact Factor: 17.047
2015 SCImago Journal Rankings: 7.853
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTsui, TYen_HK
dc.contributor.authorWu, Xen_HK
dc.contributor.authorLau, CKen_HK
dc.contributor.authorHo, DWYen_HK
dc.contributor.authorXu, Ten_HK
dc.contributor.authorSiu, YTen_HK
dc.contributor.authorFan, STen_HK
dc.date.accessioned2010-09-06T08:53:55Z-
dc.date.available2010-09-06T08:53:55Z-
dc.date.issued2003en_HK
dc.identifier.citationCirculation, 2003, v. 107 n. 20, p. 2623-2629en_HK
dc.identifier.issn0009-7322en_HK
dc.identifier.urihttp://hdl.handle.net/10722/84520-
dc.description.abstractBackground - Allograft deterioration is the major obstacle to organ transplantation as a long-term treatment of end-stage heart failure. In this study, we transduced the antioxidant gene, heme oxygenase-1 (HO-1), to heart grafts using a recombinant adeno-associated viral vector (rAAV) in a rat heart transplantation model and investigated its potentiality in prevention of chronic graft deterioration. Methods and Results - rAAV/HO-1 was administered to heart grafts through the coronary arteries during cold preservation. We investigated the expression patterns and activities of transgene, graft survival, graft histomorphology, and relevance of HO-1 expression on graft survival and chronic graft deterioration by itself. Long-term allograft survival can be achieved by rAAV/HO-1-mediated stable transgene expression. The development of graft arteriosclerosis and interstitial fibrosis was prevented in rAAV/HO-1-transduced allografts on day 100. rAAV/HO-1-mediated long-term graft protection was accompanied by remarkable downregulation of the intragraft mRNA level of macrophage migration inhibitory factor, tumor necrosis factor-α, and transforming growth factor-β1. Blockage of HO activities by zinc protoporphyrin IX at different posttransplant phases showed that the stable expression of HO-1 is a prerequisite for both survival of grafts and prevention of graft arteriosclerosis. Conclusions - rAAV/HO-1 gene transfer represents a novel therapeutic approach to prevent chronic allograft deterioration in clinical heart transplantation.en_HK
dc.languageengen_HK
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://circ.ahajournals.orgen_HK
dc.relation.ispartofCirculationen_HK
dc.rightsCirculation. Copyright © Lippincott Williams & Wilkins.en_HK
dc.subjectArteriosclerosisen_HK
dc.subjectGene therapyen_HK
dc.subjectGraftingen_HK
dc.subjectRemodelingen_HK
dc.subjectTransplantationen_HK
dc.titlePrevention of chronic deterioration of heart allograft by recombinant adeno-associated virus-mediated heme oxygenase-1 gene transferen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0009-7322&volume=107&spage=2623&epage=2629&date=2003&atitle=Prevention+of+chronic+deterioration+of+heart+allograft+by+recombinant+adeno-associated+virus-mediated+heme+oxygenase-1+gene+transferen_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.pmid12732603-
dc.identifier.scopuseid_2-s2.0-0037674918en_HK
dc.identifier.hkuros79153en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0037674918&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume107en_HK
dc.identifier.issue20en_HK
dc.identifier.spage2623en_HK
dc.identifier.epage2629en_HK
dc.identifier.isiWOS:000183165900022-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridTsui, TY=7006622455en_HK
dc.identifier.scopusauthoridWu, X=7408231534en_HK
dc.identifier.scopusauthoridLau, CK=7401968442en_HK
dc.identifier.scopusauthoridHo, DWY=7402971906en_HK
dc.identifier.scopusauthoridXu, T=7401627167en_HK
dc.identifier.scopusauthoridSiu, YT=8953557400en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK

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