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dc.contributor.authorPadrón Barthe, Laura
dc.contributor.authorVillalba Orero, María
dc.contributor.authorGómez Salinero, Jesús M.
dc.contributor.authorAcín Pérez, Rebeca
dc.contributor.authorCogliati, Sara
dc.contributor.authorLópez Olañeta, Marina
dc.contributor.authorOrtiz Sánchez, Paula
dc.contributor.authorBonzón Kulichenko, Elena
dc.contributor.authorVázquez, Jesús
dc.contributor.authorGarcía Pavía, Pablo 
dc.contributor.authorRosenthal, Nadia
dc.contributor.authorEnríquez, José Antonio
dc.contributor.authorLaza Pezzi, Enrique
dc.date.accessioned2018-11-22T12:18:58Z
dc.date.available2018-11-22T12:18:58Z
dc.date.issued2018
dc.identifier.issn0735-1097spa
dc.identifier.urihttp://hdl.handle.net/10641/1536
dc.description.abstractBACKGROUND In response to pressure overload, the heart develops ventricular hypertrophy that progressively decompensates and leads to heart failure. This pathological hypertrophy is mediated, among others, by the phosphatase calcineurin and is characterized by metabolic changes that impair energy production by mitochondria. OBJECTIVES The authors aimed to determine the role of the calcineurin splicing variant CnAb1 in the context of cardiac hypertrophy and its mechanism of action. METHODS Transgenic mice overexpressing CnAb1 specifically in cardiomyocytes and mice lacking the unique C-terminal domain in CnAb1 (CnAb1Di12 mice) were used. Pressure overload hypertrophy was induced by transaortic constriction. Cardiac function was measured by echocardiography. Mice were characterized using various molecular analyses. RESULTS In contrast to other calcineurin isoforms, the authors show here that cardiac-specific overexpression of CnAb1 in transgenic mice reduces cardiac hypertrophy and improves cardiac function. This effect is mediated by activation of serine and one-carbon metabolism, and the production of antioxidant mediators that prevent mitochondrial protein oxidation and preserve ATP production. The induction of enzymes involved in this metabolic pathway by CnAb1 is dependent on mTOR activity. Inhibition of serine and one-carbon metabolism blocks the beneficial effects of CnAb1. CnAb1Di12 mice show increased cardiac hypertrophy and declined contractility. CONCLUSIONS The metabolic reprogramming induced by CnAb1 redefines the role of calcineurin in the heart and shows for the first time that activation of the serine and one-carbon pathway has beneficial effects on cardiac hypertrophy and function, paving the way for new therapeutic approaches.spa
dc.language.isoengspa
dc.publisherJournal of the American College of Cardiologyspa
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 España*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/*
dc.subjectCardiac functionspa
dc.subjectCell signalingspa
dc.subjectHypertrophyspa
dc.subjectMetabolismspa
dc.titleActivation of Serine One-Carbon Metabolism by Calcineurin Ab1 Reduces Myocardial Hypertrophy and Improves Ventricular Function.spa
dc.typearticlespa
dc.description.versionpost-printspa
dc.rights.accessRightsopenAccessspa
dc.description.extent3325 KBspa
dc.identifier.doi10.1016/j.jacc.2017.11.067spa


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