Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice

Autores
Monnerat, Gustavo; Alarcón, Micaela L.; Vasconcellos, Luiz R.; Hochman Mendez, Camila; Brasil, Guilherme; Bassani, Rosana A.; Casis, Oscar; Malan, Daniela; Travassos, Leonardo H.; Sepúlveda, Marisa Noemí; Burgos, Juan Ignacio; Vila Petroff, Martín Gerardo; Dutra, Fabiano F.; Bozza, Marcelo T.; Paiva, Claudia N.; Bustos Carvalho, Adriana; Bonomo, Adriana; Fleischmann, Bernd K.; Campos de Carvalho, Antonio Carlos; Medei, Emiliano
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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-1β in DM mice. IL-1β 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-1β-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-1β axis with either IL-1 receptor antagonist or by inhibiting the NLRP3 inflammasome. Our results establish IL-1β as an inflammatory connection between metabolic dysfunction and arrhythmias in DM.
Facultad de Ciencias Médicas
Centro de Investigaciones Cardiovasculares
Materia
Ciencias Médicas
Ciencias Exactas
Diabetes Mellitus
IL-1β
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/85910
Acceder
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network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic miceMonnerat, GustavoAlarcón, Micaela L.Vasconcellos, Luiz R.Hochman Mendez, CamilaBrasil, GuilhermeBassani, Rosana A.Casis, OscarMalan, DanielaTravassos, Leonardo H.Sepúlveda, Marisa NoemíBurgos, Juan IgnacioVila Petroff, Martín GerardoDutra, Fabiano F.Bozza, Marcelo T.Paiva, Claudia N.Bustos Carvalho, AdrianaBonomo, AdrianaFleischmann, Bernd K.Campos de Carvalho, Antonio CarlosMedei, EmilianoCiencias MédicasCiencias ExactasDiabetes MellitusIL-1βDiabetes 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-1β in DM mice. IL-1β 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-1β-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-1β axis with either IL-1 receptor antagonist or by inhibiting the NLRP3 inflammasome. Our results establish IL-1β as an inflammatory connection between metabolic dysfunction and arrhythmias in DM.Facultad de Ciencias MédicasCentro de Investigaciones Cardiovasculares2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://sedici.unlp.edu.ar/handle/10915/85910enginfo:eu-repo/semantics/altIdentifier/issn/2041-1723info:eu-repo/semantics/altIdentifier/doi/10.1038/ncomms13344info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:16:44Zoai:sedici.unlp.edu.ar:10915/85910Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:16:44.543SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice
title Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice
spellingShingle Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice
Monnerat, Gustavo
Ciencias Médicas
Ciencias Exactas
Diabetes Mellitus
IL-1β
title_short Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice
title_full Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice
title_fullStr Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice
title_full_unstemmed Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice
title_sort Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice
dc.creator.none.fl_str_mv Monnerat, Gustavo
Alarcón, Micaela L.
Vasconcellos, Luiz R.
Hochman Mendez, Camila
Brasil, Guilherme
Bassani, Rosana A.
Casis, Oscar
Malan, Daniela
Travassos, Leonardo H.
Sepúlveda, Marisa Noemí
Burgos, Juan Ignacio
Vila Petroff, Martín Gerardo
Dutra, Fabiano F.
Bozza, Marcelo T.
Paiva, Claudia N.
Bustos Carvalho, Adriana
Bonomo, Adriana
Fleischmann, Bernd K.
Campos de Carvalho, Antonio Carlos
Medei, Emiliano
author Monnerat, Gustavo
author_facet Monnerat, Gustavo
Alarcón, Micaela L.
Vasconcellos, Luiz R.
Hochman Mendez, Camila
Brasil, Guilherme
Bassani, Rosana A.
Casis, Oscar
Malan, Daniela
Travassos, Leonardo H.
Sepúlveda, Marisa Noemí
Burgos, Juan Ignacio
Vila Petroff, Martín Gerardo
Dutra, Fabiano F.
Bozza, Marcelo T.
Paiva, Claudia N.
Bustos Carvalho, Adriana
Bonomo, Adriana
Fleischmann, Bernd K.
Campos de Carvalho, Antonio Carlos
Medei, Emiliano
author_role author
author2 Alarcón, Micaela L.
Vasconcellos, Luiz R.
Hochman Mendez, Camila
Brasil, Guilherme
Bassani, Rosana A.
Casis, Oscar
Malan, Daniela
Travassos, Leonardo H.
Sepúlveda, Marisa Noemí
Burgos, Juan Ignacio
Vila Petroff, Martín Gerardo
Dutra, Fabiano F.
Bozza, Marcelo T.
Paiva, Claudia N.
Bustos Carvalho, Adriana
Bonomo, Adriana
Fleischmann, Bernd K.
Campos de Carvalho, Antonio Carlos
Medei, Emiliano
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Médicas
Ciencias Exactas
Diabetes Mellitus
IL-1β
topic Ciencias Médicas
Ciencias Exactas
Diabetes Mellitus
IL-1β
dc.description.none.fl_txt_mv 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-1β in DM mice. IL-1β 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-1β-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-1β axis with either IL-1 receptor antagonist or by inhibiting the NLRP3 inflammasome. Our results establish IL-1β as an inflammatory connection between metabolic dysfunction and arrhythmias in DM.
Facultad de Ciencias Médicas
Centro de Investigaciones Cardiovasculares
description 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-1β in DM mice. IL-1β 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-1β-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-1β axis with either IL-1 receptor antagonist or by inhibiting the NLRP3 inflammasome. Our results establish IL-1β as an inflammatory connection between metabolic dysfunction and arrhythmias in DM.
publishDate 2016
dc.date.none.fl_str_mv 2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/85910
url http://sedici.unlp.edu.ar/handle/10915/85910
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/2041-1723
info:eu-repo/semantics/altIdentifier/doi/10.1038/ncomms13344
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
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reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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