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Role of NOD1 in Heart Failure Progression via Regulation of Ca2+ Handling.
dc.contributor.author | Val-Blasco, A. | |
dc.contributor.author | Garcia Miguel Piedras, María José | |
dc.contributor.author | Ruiz-Hurtado, G. | |
dc.contributor.author | Suárez, N. | |
dc.contributor.author | Prieto, P. | |
dc.contributor.author | González Ramos, S. | |
dc.contributor.author | Gómez Hurtado, N. | |
dc.contributor.author | Delgado, C. | |
dc.contributor.author | Pereira, L. | |
dc.contributor.author | Benito, G. | |
dc.contributor.author | Zaragoza Sánchez, Carlos | |
dc.contributor.author | Domenech, N. | |
dc.contributor.author | Crespo Leiro, M. | |
dc.contributor.author | Vasquez Echeverri, D. | |
dc.contributor.author | Núñez, G. | |
dc.contributor.author | López Collazo, E. | |
dc.contributor.author | Boscá, L. | |
dc.contributor.author | Fernández Velasco, M. | |
dc.date.accessioned | 2019-11-16T12:25:00Z | |
dc.date.available | 2019-11-16T12:25:00Z | |
dc.date.issued | 2017 | |
dc.identifier.issn | 0735-1097 | spa |
dc.identifier.uri | http://hdl.handle.net/10641/1737 | |
dc.description.abstract | BACKGROUND: 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.iso | eng | spa |
dc.publisher | Journal of the American College of Cardiology | spa |
dc.rights | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.subject | Calcium | spa |
dc.subject | Cardiac arrhythmia | spa |
dc.subject | Cardiac dysfunction | spa |
dc.subject | Innate immune system | spa |
dc.subject | Myocardial infarction | spa |
dc.subject | Ryanodine receptor | spa |
dc.title | Role of NOD1 in Heart Failure Progression via Regulation of Ca2+ Handling. | spa |
dc.type | journal article | spa |
dc.type.hasVersion | AM | spa |
dc.rights.accessRights | open access | spa |
dc.identifier.doi | 10.1016/j.jacc.2016.10.073 | spa |
dc.relation.publisherversion | https://www.sciencedirect.com/science/article/pii/S0735109716371352?via%3Dihub | spa |
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