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dc.date.accessioned | 2020-05-20T14:20:02Z | |
dc.date.available | 2020-05-20T14:20:02Z | |
dc.date.issued | 2016-01 | |
dc.identifier.uri | http://sedici.unlp.edu.ar/handle/10915/96349 | |
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. | en |
dc.format.extent | 394-406 | es |
dc.language | en | es |
dc.subject | Arrhythmias | es |
dc.subject | Prediabetes | es |
dc.subject | Impaired glucose tolerance | es |
dc.subject | Camkii | es |
dc.subject | Ryanodine receptor | es |
dc.title | Ryanodine receptor phosphorylation by CaMKII promotes spontaneous Ca2+ release events in a rodent model of early stage diabetes: The arrhythmogenic substrate | en |
dc.type | Articulo | es |
sedici.identifier.uri | https://ri.conicet.gov.ar/11336/12294 | es |
sedici.identifier.uri | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872299/ | es |
sedici.identifier.other | http://dx.doi.org/10.1016/j.ijcard.2015.09.022 | es |
sedici.identifier.other | hdl:11336/12294 | es |
sedici.identifier.issn | 0167-5273 | es |
sedici.creator.person | Sommese, Leandro Matías | es |
sedici.creator.person | Valverde, Carlos Alfredo | es |
sedici.creator.person | Blanco, Paula Graciela | es |
sedici.creator.person | Castro, María Cecilia | es |
sedici.creator.person | Vélez Rueda, Jorge Omar | es |
sedici.creator.person | Kaetzel, Marcia | es |
sedici.creator.person | Dedman, John | es |
sedici.creator.person | Anderson, Mark E. | es |
sedici.creator.person | Mattiazzi, Ramona Alicia | es |
sedici.creator.person | Palomeque, Julieta | es |
sedici.subject.materias | Ciencias Médicas | es |
sedici.description.fulltext | true | es |
mods.originInfo.place | Centro de Investigaciones Cardiovasculares | es |
mods.originInfo.place | Facultad de Ciencias Veterinarias | es |
mods.originInfo.place | Centro de Endocrinología Experimental y Aplicada | es |
sedici.subtype | Preprint | es |
sedici.rights.license | Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) | |
sedici.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | |
sedici.description.peerReview | peer-review | es |
sedici.relation.journalTitle | International Journal Of Cardiology | es |
sedici.relation.journalVolumeAndIssue | vol. 202 | es |