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dc.contributor.author
Jin, Hongwei
dc.contributor.author
Hadri, Lahouaria
dc.contributor.author
Palomeque, Julieta
dc.contributor.author
Morel, Charlotte
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Karakikes, Ioannis
dc.contributor.author
Kaprielian, Roger
dc.contributor.author
Hajjar, Roger
dc.contributor.author
Lebeche, Djamel
dc.date.available
2018-10-11T13:52:56Z
dc.date.issued
2010-06
dc.identifier.citation
Jin, Hongwei; Hadri, Lahouaria; Palomeque, Julieta; Morel, Charlotte; Karakikes, Ioannis; et al.; KChIP2 attenuates cardiac hypertrophy through regulation of Ito and intracellular; Academic Press Ltd - Elsevier Science Ltd; Journal of Molecular and Cellular Cardiology; 48; 6; 6-2010; 1169-1179
dc.identifier.issn
0022-2828
dc.identifier.uri
http://hdl.handle.net/11336/62160
dc.description.abstract
Recent evidence shows that the auxiliary subunit KChIP2, which assembles with pore-forming Kv4-subunits, represents a new potential regulator of the cardiac calcium-independent transient outward potassium current (Ito) density. In hypertrophy and heart failure, KChIP2 expression has been found to be significantly decreased. Our aim was to examine the role of KChIP2 in cardiac hypertrophy and the effect of restoring its expression on electrical remodeling and cardiac mechanical function using a combination of molecular, biochemical and gene targeting approaches. KChIP2 overexpression through gene transfer of Ad.KChIP2 in neonatal cardiomyocytes resulted in a significant increase in Ito-channel forming Kv4.2 and Kv4.3 protein levels. In vivo gene transfer of KChIP2 in aortic banded adult rats showed that, compared to sham-operated or Ad.β-gal-transduced hearts, KChIP2 significantly attenuated the developed left ventricular hypertrophy, robustly increased Ito densities, shortened action potential duration, and significantly altered myocyte mechanics by shortening contraction amplitudes and maximal rates of contraction and relaxation velocities and decreasing Ca2+ transients. Interestingly, blocking Ito with 4-aminopyridine in KChIP2-overexpressing adult cardiomyocytes significantly increased the Ca2+ transients to control levels. One-day-old rat pups intracardially transduced with KChIP2 for twomonths then subjected to aortic banding for 6-8weeks (to induce hypertrophy) showed similar echocardiographic, electrical and mechanical remodeling parameters. In addition, in cultured adult cardiomyocytes, KChIP2 overexpression increased the expression of Ca2+-ATPase (SERCA2a) and sodium calcium exchanger but had no effect on ryanodine receptor 2 or phospholamban expression. In neonatal myocytes, KChIP2 notably reversed Ang II-induced hypertrophic changes in protein synthesis and MAP-kinase activation. It also significantly decreased calcineurin expression, NFATc1 expression and nuclear translocation and its downstream target, MCiP1.4. Altogether, these data show that KChIP2 can attenuate cardiac hypertrophy possibly through modulation of intracellular calcium concentration and calcineurin/NFAT pathway. © 2009.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Academic Press Ltd - Elsevier Science Ltd
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Cardiac Contractility
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Cardiac Hypertrophy
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Gene Transfer
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Kchip2
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Kv4 Channels
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Inmunología
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
KChIP2 attenuates cardiac hypertrophy through regulation of Ito and intracellular
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-09-10T16:44:10Z
dc.journal.volume
48
dc.journal.number
6
dc.journal.pagination
1169-1179
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Jin, Hongwei. Mount Sinai School of Medicine; Estados Unidos
dc.description.fil
Fil: Hadri, Lahouaria. Mount Sinai School of Medicine; Estados Unidos
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Fil: Palomeque, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
dc.description.fil
Fil: Morel, Charlotte. Mount Sinai School of Medicine; Estados Unidos
dc.description.fil
Fil: Karakikes, Ioannis. Mount Sinai School of Medicine; Estados Unidos
dc.description.fil
Fil: Kaprielian, Roger. AMGEN; Canadá
dc.description.fil
Fil: Hajjar, Roger. Mount Sinai School of Medicine; Estados Unidos
dc.description.fil
Fil: Lebeche, Djamel. Mount Sinai School of Medicine; Estados Unidos
dc.journal.title
Journal of Molecular and Cellular Cardiology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1016/j.yjmcc.2009.12.019
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S002228280900563X
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