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

Autores
Ennis, Irene Lucía; Li, Ronald A.; Murphy, Anne M.; Marbán, Eduardo; Nuss, H. Bradley
Año de publicación
2002
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Heart 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.
Facultad de Ciencias Médicas
Centro de Investigaciones Cardiovasculares
Materia
Ciencias Médicas
Dual gene therapy
excitation
contractility
Heart failure
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/84675
Acceder
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oai_identifier_str oai:sedici.unlp.edu.ar:10915/84675
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractilityEnnis, Irene LucíaLi, Ronald A.Murphy, Anne M.Marbán, EduardoNuss, H. BradleyCiencias MédicasDual gene therapyexcitationcontractilityHeart failureHeart 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.Facultad de Ciencias MédicasCentro de Investigaciones Cardiovasculares2002info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf393-400http://sedici.unlp.edu.ar/handle/10915/84675enginfo:eu-repo/semantics/altIdentifier/issn/0021-9738info:eu-repo/semantics/altIdentifier/doi/10.1172/JCI0213359info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:16:16Zoai:sedici.unlp.edu.ar:10915/84675Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:16:16.323SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility
title Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility
spellingShingle Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility
Ennis, Irene Lucía
Ciencias Médicas
Dual gene therapy
excitation
contractility
Heart failure
title_short Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility
title_full Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility
title_fullStr Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility
title_full_unstemmed Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility
title_sort Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility
dc.creator.none.fl_str_mv Ennis, Irene Lucía
Li, Ronald A.
Murphy, Anne M.
Marbán, Eduardo
Nuss, H. Bradley
author Ennis, Irene Lucía
author_facet Ennis, Irene Lucía
Li, Ronald A.
Murphy, Anne M.
Marbán, Eduardo
Nuss, H. Bradley
author_role author
author2 Li, Ronald A.
Murphy, Anne M.
Marbán, Eduardo
Nuss, H. Bradley
author2_role author
author
author
author
dc.subject.none.fl_str_mv Ciencias Médicas
Dual gene therapy
excitation
contractility
Heart failure
topic Ciencias Médicas
Dual gene therapy
excitation
contractility
Heart failure
dc.description.none.fl_txt_mv Heart 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.
Facultad de Ciencias Médicas
Centro de Investigaciones Cardiovasculares
description Heart 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.
publishDate 2002
dc.date.none.fl_str_mv 2002
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/84675
url http://sedici.unlp.edu.ar/handle/10915/84675
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/0021-9738
info:eu-repo/semantics/altIdentifier/doi/10.1172/JCI0213359
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
393-400
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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score 13.070432

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