Artículo
Ryanodine receptor phosphorylation by CaMKII promotes spontaneous Ca2+ release events in a rodent model of early stage diabetes: The arrhythmogenic substrate
Sommese, Leandro Matías
; Valverde, Carlos Alfredo
; Blanco, Paula Graciela
; Castro, María Cecilia
; Velez Rueda, Jorge Omar
; Kaetzel, Marcia; Dedman, John; Anderson, Mark E.; Mattiazzi, Ramona Alicia
; Palomeque, Julieta







Fecha de publicación:
01/2016
Editorial:
Elsevier Ireland
Revista:
International Journal Of Cardiology
ISSN:
0167-5273
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Resumen
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.
Archivos asociados
http://dx.doi.org/10.1016/j.ijcard.2015.09.022
http://www.sciencedirect.com/science/article/pii/S0167527315304630
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872299/
http://www.sciencedirect.com/science/article/pii/S0167527315304630
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872299/

Citación:
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
Comunidades y colecciones
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Articulos(CENEXA) [64]
Articulos de CENTRO DE ENDOCRINOLOGIA EXP.Y APLICADA (I) -
Articulos(CCT - LA PLATA) [4066]
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - LA PLATA -
Articulos(CIC) [123]
Articulos de CENTRO DE INVEST.CARDIOVASCULARES (I)