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dc.creatorSommese, Leandro Matías-
dc.creatorValverde, Carlos Alfredo-
dc.creatorBlanco, Paula Graciela-
dc.creatorCastro, María Cecilia-
dc.creatorVelez Rueda, Jorge Omar-
dc.creatorKaetzel, Marcia-
dc.creatorDedman, John-
dc.creatorAnderson, Mark E.-
dc.creatorMattiazzi, Ramona Alicia-
dc.creatorPalomeque, Julieta-
dc.date2017-02-01T13:36:12Z-
dc.date2017-02-01T13:36:12Z-
dc.date2016-01-
dc.date2017-01-27T14:16:28Z-
dc.date.accessioned2019-04-29T15:34:51Z-
dc.date.available2019-04-29T15:34:51Z-
dc.date.issued2017-02-01T13:36:12Z-
dc.date.issued2017-02-01T13:36:12Z-
dc.date.issued2016-01-
dc.date.issued2017-01-27T14:16:28Z-
dc.identifierSommese, 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.identifier0167-5273-
dc.identifierhttp://hdl.handle.net/11336/12294-
dc.identifier.urihttp://rodna.bn.gov.ar:8080/jspui/handle/bnmm/297072-
dc.descriptionBackground: 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.descriptionFil: 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.descriptionFil: 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.descriptionFil: Blanco, Paula Graciela. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina-
dc.descriptionFil: 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.descriptionFil: 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.descriptionFil: Kaetzel, Marcia. University Of Cincinnati; Estados Unidos-
dc.descriptionFil: Dedman, John. University Of Cincinnati; Estados Unidos-
dc.descriptionFil: Anderson, Mark E.. University of Iowa; Estados Unidos-
dc.descriptionFil: 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.descriptionFil: 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-
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dc.languageeng-
dc.publisherElsevier Ireland-
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.ijcard.2015.09.022-
dc.relationinfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0167527315304630-
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872299/-
dc.rightsinfo:eu-repo/semantics/openAccess-
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/-
dc.sourcereponame:CONICET Digital (CONICET)-
dc.sourceinstname:Consejo Nacional de Investigaciones Científicas y Técnicas-
dc.sourceinstacron:CONICET-
dc.subjectARRHYTHMIAS-
dc.subjectPREDIABETES-
dc.subjectIMPAIRED GLUCOSE TOLERANCE-
dc.subjectCaMKII-
dc.subjectRYANODINE RECEPTOR-
dc.subjectSistemas Cardíaco y Cardiovascular-
dc.subjectMedicina Clínica-
dc.subjectCIENCIAS MÉDICAS Y DE LA SALUD-
dc.titleRyanodine receptor phosphorylation by CaMKII promotes spontaneous Ca2+ release events in a rodent model of early stage diabetes: The arrhythmogenic substrate-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.typeinfo:ar-repo/semantics/articulo-
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