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dc.contributor.authorVal-Blasco, A.
dc.contributor.authorGarcia Miguel Piedras, María José 
dc.contributor.authorRuiz-Hurtado, G.
dc.contributor.authorSuárez, N.
dc.contributor.authorPrieto, P.
dc.contributor.authorGonzález Ramos, S.
dc.contributor.authorGómez Hurtado, N.
dc.contributor.authorDelgado, C.
dc.contributor.authorPereira, L.
dc.contributor.authorBenito, G.
dc.contributor.authorZaragoza Sánchez, Carlos 
dc.contributor.authorDomenech, N.
dc.contributor.authorCrespo Leiro, M.
dc.contributor.authorVasquez Echeverri, D.
dc.contributor.authorNúñez, G.
dc.contributor.authorLópez Collazo, E.
dc.contributor.authorBoscá, L.
dc.contributor.authorFernández Velasco, M.
dc.date.accessioned2019-11-16T12:25:00Z
dc.date.available2019-11-16T12:25:00Z
dc.date.issued2017
dc.identifier.issn0735-1097spa
dc.identifier.urihttp://hdl.handle.net10641/1737
dc.description.abstractBACKGROUND: Heart failure (HF) is a complex syndrome associated with a maladaptive innate immune system response that leads to deleterious cardiac remodeling. However, the underlying mechanisms of this syndrome are poorly understood. Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a newly recognized innate immune sensor involved in cardiovascular diseases. OBJECTIVES: This study evaluated the role of NOD1 in HF progression. METHODS: NOD1 was examined in human failing myocardium and in a post-myocardial infarction (PMI) HF model evaluated in wild-type (wt-PMI) and Nod1-/- mice (Nod1-/--PMI). RESULTS: The NOD1 pathway was up-regulated in human and murine failing myocardia. Compared with wt-PMI, hearts from Nod1-/--PMI mice had better cardiac function and attenuated structural remodeling. Ameliorated cardiac function in Nod1-/--PMI mice was associated with prevention of Ca2+ dynamic impairment linked to HF, including smaller and longer intracellular Ca2+ concentration transients and a lesser sarcoplasmic reticulum Ca2+ load due to a down-regulation of the sarcoplasmic reticulum Ca2+-adenosine triphosphatase pump and by augmented levels of the Na+/Ca2+ exchanger. Increased diastolic Ca2+ release in wt-PMI cardiomyocytes was related to hyperphosphorylation of ryanodine receptors, which was blunted in Nod1-/--PMI cardiomyocytes. Pharmacological blockade of NOD1 also prevented Ca2+ mishandling in wt-PMI mice. Nod1-/--PMI mice showed significantly fewer ventricular arrhythmias and lower mortality after isoproterenol administration. These effects were associated with lower aberrant systolic Ca2+ release and with a prevention of the hyperphosphorylation of ryanodine receptors under isoproterenol administration in Nod1-/--PMI mice. CONCLUSIONS: NOD1 modulated intracellular Ca2+ mishandling in HF, emerging as a new target for HF therapy.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.subjectCalciumspa
dc.subjectCardiac arrhythmiaspa
dc.subjectCardiac dysfunctionspa
dc.subjectInnate immune systemspa
dc.subjectMyocardial infarctionspa
dc.subjectRyanodine receptorspa
dc.titleRole of NOD1 in Heart Failure Progression via Regulation of Ca2+ Handling.spa
dc.typearticlespa
dc.description.versionpost-printspa
dc.rights.accessRightsopenAccessspa
dc.identifier.doi10.1016/j.jacc.2016.10.073spa
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S0735109716371352?via%3Dihubspa


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Atribución-NoComercial-SinDerivadas 3.0 España
Except where otherwise noted, this item's license is described as Atribución-NoComercial-SinDerivadas 3.0 España