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Article: Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility

TitleDual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date2002
PublisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org
Citation
Journal Of Clinical Investigation, 2002, v. 109 n. 3, p. 393-400 How to Cite?
AbstractHeart failure is characterized by depressed contractility and delayed repolarization. The latter feature predisposes the failing heart to ventricular arrhythmias and represents a logical target for gene therapy. Unfortunately, unopposed correction of the delay in repolarization will decrease the time available for calcium cycling during each heartbeat, potentially aggravating the depression of contractility. Here we describe the development and application of a novel gene therapy strategy designed to abbreviate excitation without depressing contraction. The calcium ATPase SERCA1 was coexpressed with the potassium channel Kir2.1 in guinea pig hearts. Myocytes from the hearts had bigger calcium transients and shorter action potentials. In vivo, repolarization was abbreviated, but contractile function remained unimpaired. Dual gene therapy of the sort described here can be generalized to exploit opposing or synergistic therapeutic principles to achieve a tailored phenotype.
Persistent Identifierhttp://hdl.handle.net/10722/91556
ISSN
2015 Impact Factor: 12.575
2015 SCImago Journal Rankings: 8.764
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorEnnis, ILen_HK
dc.contributor.authorLi, RAen_HK
dc.contributor.authorMurphy, AMen_HK
dc.contributor.authorMarbán, Een_HK
dc.contributor.authorBradley Nuss, Hen_HK
dc.date.accessioned2010-09-17T10:21:18Z-
dc.date.available2010-09-17T10:21:18Z-
dc.date.issued2002en_HK
dc.identifier.citationJournal Of Clinical Investigation, 2002, v. 109 n. 3, p. 393-400en_HK
dc.identifier.issn0021-9738en_HK
dc.identifier.urihttp://hdl.handle.net/10722/91556-
dc.description.abstractHeart failure is characterized by depressed contractility and delayed repolarization. The latter feature predisposes the failing heart to ventricular arrhythmias and represents a logical target for gene therapy. Unfortunately, unopposed correction of the delay in repolarization will decrease the time available for calcium cycling during each heartbeat, potentially aggravating the depression of contractility. Here we describe the development and application of a novel gene therapy strategy designed to abbreviate excitation without depressing contraction. The calcium ATPase SERCA1 was coexpressed with the potassium channel Kir2.1 in guinea pig hearts. Myocytes from the hearts had bigger calcium transients and shorter action potentials. In vivo, repolarization was abbreviated, but contractile function remained unimpaired. Dual gene therapy of the sort described here can be generalized to exploit opposing or synergistic therapeutic principles to achieve a tailored phenotype.en_HK
dc.languageengen_HK
dc.publisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.orgen_HK
dc.relation.ispartofJournal of Clinical Investigationen_HK
dc.subjectChemicals And Cas Registry Numbersen_HK
dc.subject.meshAction Potentialsen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshArrhythmias, Cardiac - etiology - physiopathology - therapyen_HK
dc.subject.meshCalcium Signalingen_HK
dc.subject.meshCalcium-Transporting ATPases - geneticsen_HK
dc.subject.meshEchocardiographyen_HK
dc.subject.meshElectrocardiographyen_HK
dc.subject.meshElectrophysiologyen_HK
dc.subject.meshGene Expressionen_HK
dc.subject.meshGene Therapy - methodsen_HK
dc.subject.meshGuinea Pigsen_HK
dc.subject.meshHeart Failure - complications - physiopathology - therapyen_HK
dc.subject.meshMyocardial Contractionen_HK
dc.subject.meshMyocardium - metabolismen_HK
dc.subject.meshPotassium Channels, Inwardly Rectifying - geneticsen_HK
dc.subject.meshSarcoplasmic Reticulum Calcium-Transporting ATPasesen_HK
dc.titleDual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractilityen_HK
dc.typeArticleen_HK
dc.identifier.emailLi, RA:ronaldli@hkucc.hku.hken_HK
dc.identifier.authorityLi, RA=rp01352en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1172/JCI200213359en_HK
dc.identifier.pmid11827999-
dc.identifier.scopuseid_2-s2.0-0036173169en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036173169&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume109en_HK
dc.identifier.issue3en_HK
dc.identifier.spage393en_HK
dc.identifier.epage400en_HK
dc.identifier.isiWOS:000173710500014-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridEnnis, IL=6604033332en_HK
dc.identifier.scopusauthoridLi, RA=7404724466en_HK
dc.identifier.scopusauthoridMurphy, AM=7401451778en_HK
dc.identifier.scopusauthoridMarbán, E=8075977300en_HK
dc.identifier.scopusauthoridBradley Nuss, H=19033613300en_HK

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