Macrophage-dependent IL-1 beta production induces cardiac arrhythmias in diabetic mice
dc.contributor.author | Monnerat, Gustavo | |
dc.contributor.author | Alarcón, Micaela L. | |
dc.contributor.author | Vasconcellos, Luiz R. | |
dc.contributor.author | Hochman-Mendez, Camila | |
dc.contributor.author | Brasil, Guilherme | |
dc.contributor.author | Bassani, Rosana A. | |
dc.contributor.author | Casis Sáenz, Oscar | |
dc.contributor.author | Malan, Daniela | |
dc.contributor.author | Travassos, Leonardo H. | |
dc.contributor.author | Sepúlveda, Marisa | |
dc.contributor.author | Burgos, Juan Ignacio | |
dc.contributor.author | Vila Petroff, Martin | |
dc.contributor.author | Dutra, Fabiano F. | |
dc.contributor.author | Bozza, Marcelo T. | |
dc.contributor.author | Paiva, Claudia N. | |
dc.contributor.author | Bastos Carvalho, Adriana | |
dc.contributor.author | Bonomo, Adriana | |
dc.contributor.author | Fleischmann, Bernd K. | |
dc.contributor.author | Campos de Carvalho, Antonio Carlos | |
dc.contributor.author | Medei, Emiliano | |
dc.date.accessioned | 2018-03-16T09:10:50Z | |
dc.date.available | 2018-03-16T09:10:50Z | |
dc.date.issued | 2016-11-24 | |
dc.identifier.citation | Nature Communications 7 : (2016) // Article ID 13344 | es_ES |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | http://hdl.handle.net/10810/25728 | |
dc.description.abstract | Diabetes mellitus (DM) encompasses a multitude of secondary disorders, including heart disease. One of the most frequent and potentially life threatening disorders of DM-induced heart disease is ventricular tachycardia (VT). Here we show that toll-like receptor 2 (TLR2) and NLRP3 inflammasome activation in cardiac macrophages mediate the production of IL-1 beta in DM mice. IL-1 beta causes prolongation of the action potential duration, induces a decrease in potassium current and an increase in calcium sparks in cardiomyocytes, which are changes that underlie arrhythmia propensity. IL-1 beta-induced spontaneous contractile events are associated with CaMKII oxidation and phosphorylation. We further show that DM-induced arrhythmias can be successfully treated by inhibiting the IL-1 beta axis with either IL-1 receptor antagonist or by inhibiting the NLRP3 inflammasome. Our results establish IL-1 beta as an inflammatory connection between metabolic dysfunction and arrhythmias in DM. | es_ES |
dc.description.sponsorship | This work was funded by the Brazilian National Research Council (CNPq, grants: 308168/2012-7 and 475218/2012-4), the Carlos Chagas Filho Rio de Janeiro State Research Foundation (FAPERJ, grants: E-26/103.222/2011 and E-26/111.171/2011) and National Institutes of Science and Technology for Biology Structural and Bioimaging (grant: 573767/2008-4), Brazil and by grants of the Deutsche Forschungsgemeinschaft (FL 276/7-2 to B.K.F.) and by the Stem Cell Factory II co-founded by the European Union (European Regional Development Fund-Investing in your future) and the German federal state North Rhine-Westphalia (NRW) (to D.M. and B.K.F.). Additionally, the work was funded by PICT 1678 from FONCYT to M.V.-P.. G.M. has a postdoctoral fellowship from FAPERJ (PDR 10), F.F.D has a postdoctoral fellowship from CAPES, L.R.V. has a PhD fellowship from FAPERJ, M.L.A has a PhD fellowship from CNPq. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Publishing | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | toll-like receptors | es_ES |
dc.subject | NLRP3 inflammasome | es_ES |
dc.subject | sarcoplasmic-reticulum | es_ES |
dc.subject | ventricular repolarization | es_ES |
dc.subject | myocardial-infarction | es_ES |
dc.subject | insulin-resistance | es_ES |
dc.subject | NALP3 inflammasome | es_ES |
dc.subject | converting-enzyme | es_ES |
dc.subject | human monocytes | es_ES |
dc.subject | activation | es_ES |
dc.title | Macrophage-dependent IL-1 beta production induces cardiac arrhythmias in diabetic mice | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0 | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://www.nature.com/articles/ncomms13344 | es_ES |
dc.identifier.doi | 10.1038/ncomms13344 | |
dc.departamentoes | Fisiología | es_ES |
dc.departamentoeu | Fisiologia | es_ES |
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