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

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 tim...

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Autores principales: Ennis, Irene Lucía, Li, Ronald A., Murphy, Anne M., Marbán, Eduardo, Nuss, H. Bradley
Formato: Articulo
Lenguaje:Inglés
Publicado: 2002
Materias:
Ciencias Médicas
Dual gene therapy
excitation
contractility
Heart failure
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/84675
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-84675
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Dual gene therapy
excitation
contractility
Heart failure
spellingShingle Ciencias Médicas
Dual gene therapy
excitation
contractility
Heart failure
Ennis, Irene Lucía
Li, Ronald A.
Murphy, Anne M.
Marbán, Eduardo
Nuss, H. Bradley
Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility
topic_facet Ciencias Médicas
Dual gene therapy
excitation
contractility
Heart failure
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.
format Articulo
Articulo
author Ennis, Irene Lucía
Li, Ronald A.
Murphy, Anne M.
Marbán, Eduardo
Nuss, H. Bradley
author_facet Ennis, Irene Lucía
Li, Ronald A.
Murphy, Anne M.
Marbán, Eduardo
Nuss, H. Bradley
author_sort Ennis, Irene Lucía
title Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility
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
publishDate 2002
url http://sedici.unlp.edu.ar/handle/10915/84675
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AT murphyannem dualgenetherapywithserca1andkir21abbreviatesexcitationwithoutsuppressingcontractility
AT marbaneduardo dualgenetherapywithserca1andkir21abbreviatesexcitationwithoutsuppressingcontractility
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