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

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 activa...

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Autores principales: 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
Formato: Articulo
Lenguaje:Inglés
Publicado: 2016
Materias:
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/85910
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id I19-R120-10915-85910
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Ciencias Exactas
Diabetes Mellitus
IL-1β
spellingShingle Ciencias Médicas
Ciencias Exactas
Diabetes Mellitus
IL-1β
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
Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice
topic_facet Ciencias Médicas
Ciencias Exactas
Diabetes Mellitus
IL-1β
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.
format Articulo
Articulo
author 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_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_sort Monnerat, Gustavo
title Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice
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
publishDate 2016
url http://sedici.unlp.edu.ar/handle/10915/85910
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