IL-1β production induces cardiac arrhythmias in diabetic mice

GUSTAVO MONNERAT; MEDEI EMILIANO; VILA PETROFF MARTÍN; OSCAR CASIS; MARCELO BOZZA; SEPÚLVEDA MARISA; LUIS VASCONCELLOS; ROSANA A. BASSANI; LÓPEZ ALARCÓN MICAELA; JUAN IGNACIO BURGOS; CLAUDIA PAIVA; ANTONIO CARLOS CAMPOS DE CARVALHO

Buenos Aires

Congreso; ISHR; 2016

Centro de Investigaciones Cardiovasculares "Dr. Horacio E Cingolani"

Diabetes causes a multitude of secondary disorders, which havea severe prognostic impact in heart disease and arrhythmias. Thelatter are probably due to inflammation and pathologic signaling.Herein, we investigated origin and mechanisms underlying theonset of these arrhythmias using a combination of genetic andpharmacological tools. We demonstrate that TLR2 mediates theproduction of IL-1β, which in turn induces arrhythmias. In fact,IL-1β induces longer action potential as a consequence of a decreasein potassium current (Ito). Additionally, IL-1β increase calciumsparks in cardiomyocytes. Thus, our study assigns a criticalrole to the diabetes-induced inflammation process in one of themajor secondary fatalities associated with this widespread disease.We further demonstrate that blocking the IL-1β receptor can therapeuticallytreat diabetes-induced ventricular arrhythmias.