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Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice.

ABSTRACT: 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.

SUBMITTER: Monnerat G

PROVIDER: S-EPMC5123037 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice.

Monnerat Gustavo G Alarcón Micaela L ML Vasconcellos Luiz R LR Hochman-Mendez Camila C Brasil Guilherme G Bassani Rosana A RA Casis Oscar O Malan Daniela D Travassos Leonardo H LH Sepúlveda Marisa M Burgos Juan Ignacio JI Vila-Petroff Martin M Dutra Fabiano F FF Bozza Marcelo T MT Paiva Claudia N CN Carvalho Adriana Bastos AB Bonomo Adriana A Fleischmann Bernd K BK de Carvalho Antonio Carlos Campos ACC Medei Emiliano E

Nature communications 20161124

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 s ...[more]

PMID: 27882934

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Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice.

Publications

Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice.

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