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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Detalles Bibliográficos
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, Martin Gerarde, Dutra, Fabiano F., Bozza, Marcelo T., Paiva, Claudia N., Carvalho, Adriana Bastos, Bonomo, Adriana, Fleischmann, Bernd K., Campos De Carvalho, Antonio Carlos, Medei, Emiliano
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/54407
Acceso en línea:http://hdl.handle.net/11336/54407
Access Level:acceso abierto
Palabra clave:Diabetes Mellitus
Il-1beta
Arrhythmias
Macrophage
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
Descripción
Sumario: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.

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