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

Author

Listed:
  • Gustavo Monnerat

    (Institute of Biophysics Carlos Chagas Filho, Universidade Federal do Rio de Janeiro)

  • Micaela L. Alarcón

    (Institute of Biophysics Carlos Chagas Filho, Universidade Federal do Rio de Janeiro)

  • Luiz R. Vasconcellos

    (LIRS-Laboratory of Immunoreceptors and Signaling, Universidade Federal do Rio de Janeiro
    Instituto de Microbiologia, Universidade Federal do Rio de Janeiro)

  • Camila Hochman-Mendez

    (Institute of Biophysics Carlos Chagas Filho, Universidade Federal do Rio de Janeiro)

  • Guilherme Brasil

    (Institute of Biophysics Carlos Chagas Filho, Universidade Federal do Rio de Janeiro)

  • Rosana A. Bassani

    (Center for Biomedical Engineering, University of Campinas)

  • Oscar Casis

    (Facultad de Farmacia, Universidad del País Vasco UPV/EHU)

  • Daniela Malan

    (Institute of Physiology I, Life and Brain Center, University of Bonn)

  • Leonardo H. Travassos

    (LIRS-Laboratory of Immunoreceptors and Signaling, Universidade Federal do Rio de Janeiro)

  • Marisa Sepúlveda

    (Centro de Investigaciones Cardiovasculares, Conicet La Plata, Facultad de Ciencias Médicas, Universidad Nacional de La Plata)

  • Juan Ignacio Burgos

    (Centro de Investigaciones Cardiovasculares, Conicet La Plata, Facultad de Ciencias Médicas, Universidad Nacional de La Plata)

  • Martin Vila-Petroff

    (Centro de Investigaciones Cardiovasculares, Conicet La Plata, Facultad de Ciencias Médicas, Universidad Nacional de La Plata)

  • Fabiano F. Dutra

    (Instituto de Microbiologia, Universidade Federal do Rio de Janeiro)

  • Marcelo T. Bozza

    (Instituto de Microbiologia, Universidade Federal do Rio de Janeiro)

  • Claudia N. Paiva

    (Instituto de Microbiologia, Universidade Federal do Rio de Janeiro)

  • Adriana Bastos Carvalho

    (Institute of Biophysics Carlos Chagas Filho, Universidade Federal do Rio de Janeiro)

  • Adriana Bonomo

    (Instituto de Microbiologia, Universidade Federal do Rio de Janeiro
    FIOCANCER/ VPPLR/FIOCRUZ, FIOCRUZ-Manguinhos)

  • Bernd K. Fleischmann

    (Institute of Physiology I, Life and Brain Center, University of Bonn)

  • Antonio Carlos Campos de Carvalho

    (Institute of Biophysics Carlos Chagas Filho, Universidade Federal do Rio de Janeiro
    National Center for Structural Biology and Bioimaging—CENABIO/UFRJ)

  • Emiliano Medei

    (Institute of Biophysics Carlos Chagas Filho, Universidade Federal do Rio de Janeiro
    National Center for Structural Biology and Bioimaging—CENABIO/UFRJ)

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.

Suggested Citation

  • Gustavo Monnerat & Micaela L. Alarcón & Luiz R. Vasconcellos & Camila Hochman-Mendez & Guilherme Brasil & Rosana A. Bassani & Oscar Casis & Daniela Malan & Leonardo H. Travassos & Marisa Sepúlveda & J, 2016. "Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice," Nature Communications, Nature, vol. 7(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13344
    DOI: 10.1038/ncomms13344
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