Upload resources

Upload your works to SEDICI to increase its visibility and improve its impact

 

Show simple item record

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


Download Files

This item appears in the following Collection(s)

Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) Except where otherwise noted, this item's license is described as Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)