Articulo
Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice
Registro en:
issn:2041-1723
Autor
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
Institución
Resumen
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