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 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 Cardiovasculare

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 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 Cardiovasculare

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 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.Fil: Monnerat, Gustavo. Universidade Federal do Rio de Janeiro; BrasilFil: Alarcón, Micaela L.. Universidade Federal do Rio de Janeiro; BrasilFil: Vasconcellos, Luiz R.. Universidade Federal do Rio de Janeiro; BrasilFil: Hochman-Mendez, Camila. Universidade Federal do Rio de Janeiro; BrasilFil: Brasil, Guilherme. Universidade Federal do Rio de Janeiro; BrasilFil: Bassani, Rosana A.. Universidade Estadual de Campinas; BrasilFil: Casis, Oscar. Universidad del País Vasco; EspañaFil: Malan, Daniela. Universitat Bonn; AlemaniaFil: Travassos, Leonardo H.. Universidade Federal do Rio de Janeiro; BrasilFil: Sepúlveda, Marisa Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Burgos, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Vila Petroff, Martin Gerarde. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Dutra, Fabiano F.. Universidade Federal do Rio de Janeiro; BrasilFil: Bozza, Marcelo T.. Universidade Federal do Rio de Janeiro; BrasilFil: Paiva, Claudia N.. Universidade Federal do Rio de Janeiro; BrasilFil: Carvalho, Adriana Bastos. Universidade Federal do Rio de Janeiro; BrasilFil: Bonomo, Adriana. Universidade Federal do Rio de Janeiro; Brasil. Fundación Oswaldo Cruz; BrasilFil: Fleischmann, Bernd K.. Universitat Bonn; AlemaniaFil: Campos De Carvalho, Antonio Carlos. Universidade Federal do Rio de Janeiro; BrasilFil: Medei, Emiliano. Universidade Federal do Rio de Janeiro; Brasi

Derechos Humanos desde América Latina. Discusiones y estrategias actuales

Este libro es el resultado de un proyecto colectivo, iniciado a partir de las ponencias del I Congreso de Derechos Humanos desde América Latina, realizado en la Universidad Nacional de Rosario (UNR) en agosto de 2019. Participaron del trabajo los siguientes espacios institucionales: Cátedra de Pensamiento Constitucional Latinoamericano (UNR), Instituto de Cooperación Latinoamericana (UNR), Área de Derechos Humanos (UNR) y Maestría en Derechos Humanos (UASLP).Universidad Nacional de Rosari