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dc.contributor.author
Sommese, Leandro Matías
dc.contributor.author
Valverde, Carlos Alfredo
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Blanco, Paula Graciela
dc.contributor.author
Castro, María Cecilia
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Velez Rueda, Jorge Omar
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Kaetzel, Marcia
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Dedman, John
dc.contributor.author
Anderson, Mark E.
dc.contributor.author
Mattiazzi, Ramona Alicia
dc.contributor.author
Palomeque, Julieta
dc.date.available
2017-02-01T13:36:12Z
dc.date.issued
2016-01
dc.identifier.citation
Sommese, Leandro Matías; Valverde, Carlos Alfredo; Blanco, Paula Graciela; Castro, María Cecilia; Velez Rueda, Jorge Omar; et al.; Ryanodine receptor phosphorylation by CaMKII promotes spontaneous Ca2+ release events in a rodent model of early stage diabetes: The arrhythmogenic substrate; Elsevier Ireland; International Journal Of Cardiology; 202; 1-2016; 394-406
dc.identifier.issn
0167-5273
dc.identifier.uri
http://hdl.handle.net/11336/12294
dc.description.abstract
Background: Heart failure and arrhythmias occur more frequently in patients with type 2 diabetes (T2DM) than in the general population. T2DM is preceded by a prediabetic condition marked by elevated reactive oxygen species (ROS) and subclinical cardiovascular defects. Although multifunctional Ca2+ calmodulin-dependent protein kinase II (CaMKII) is ROS-activated and CaMKII hyperactivity promotes cardiac diseases, a link between prediabetes and CaMKII in the heart is unprecedented.
Objectives: To prove the hypothesis that increased ROS and CaMKII activity contribute to heart failure and arrhythmogenic mechanisms in early stage diabetes.
Methods–Results: Echocardiography, electrocardiography, biochemical and intracellular Ca2+ (Ca2+i) determinations were performed in fructose-rich diet-induced impaired glucose tolerance, a prediabetes model, in rodents. Fructose-rich diet rats showed decreased contractility and hypertrophy associated with increased CaMKII activity, ROS production, oxidized CaMKII and enhanced CaMKII-dependent ryanodine receptor (RyR2) phosphorylation compared to rats fed with control diet. Isolated cardiomyocytes from fructose-rich diet showed increased spontaneous Ca2+i release events associated with spontaneous contractions, which were prevented by KN-93, a CaMKII inhibitor, or addition of Tempol, a ROS scavenger, to the diet. Moreover, fructose-rich diet myocytes showed increased diastolic Ca2+ during the burst of spontaneous Ca2+i release events. Mice treated with Tempol or with sarcoplasmic reticulum-targeted CaMKII-inhibition by transgenic expression of the CaMKII inhibitory peptide AIP, were protected from fructose-rich diet-induced spontaneous Ca2+i release events, spontaneous contractions and arrhythmogenesis in vivo, despite ROS increases.
Conclusions: RyR2 phosphorylation by ROS-activated CaMKII, contributes to impaired glucose tolerance-induced arrhythmogenic mechanisms, suggesting that CaMKII inhibition could prevent prediabetic cardiovascular complications and/or evolution.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier Ireland
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Arrhythmias
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Prediabetes
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Impaired Glucose Tolerance
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Camkii
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Ryanodine Receptor
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Sistemas Cardíaco y Cardiovascular
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Medicina Clínica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Ryanodine receptor phosphorylation by CaMKII promotes spontaneous Ca2+ release events in a rodent model of early stage diabetes: The arrhythmogenic substrate
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-01-27T14:16:28Z
dc.journal.volume
202
dc.journal.pagination
394-406
dc.journal.pais
Irlanda
dc.description.fil
Fil: Sommese, Leandro Matías. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
dc.description.fil
Fil: Valverde, Carlos Alfredo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
dc.description.fil
Fil: Blanco, Paula Graciela. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina
dc.description.fil
Fil: Castro, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
dc.description.fil
Fil: Velez Rueda, Jorge Omar. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
dc.description.fil
Fil: Kaetzel, Marcia. University Of Cincinnati; Estados Unidos
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Fil: Dedman, John. University Of Cincinnati; Estados Unidos
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Fil: Anderson, Mark E.. University of Iowa; Estados Unidos
dc.description.fil
Fil: Mattiazzi, Ramona Alicia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
dc.description.fil
Fil: Palomeque, Julieta. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
dc.journal.title
International Journal Of Cardiology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.ijcard.2015.09.022
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0167527315304630
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872299/
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