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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Bibliographic Details
Authors: 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
Format: article
Status:Published version
Publication Date:2016
Country:Argentina
Institution:Universidad Nacional de La Plata
Repository:SEDICI (UNLP)
Language:English
OAI Identifier:oai:sedici.unlp.edu.ar:10915/85910
Online Access:http://sedici.unlp.edu.ar/handle/10915/85910
Access Level:Open access
Keyword:Ciencias Médicas
Ciencias Exactas
Diabetes Mellitus
IL-1β
Description
Summary: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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