Published November 18, 2022 | Version v1
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IL-1β sensitization to atrial fibrillation depends on caspase-1 expression

Creators

  • 1. Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
  • 2. Laboratory of Immunopharmacology, Oswaldo Cruz Institute (IOC), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, RJ, Brazil
  • 3. Institute of Biomedical Sciences. Federal University of Rio de Janeiro
  • 4. Centro de Facilidades e Apoio à Pesquisa, CEFAP- Universidade de São Paulo (USP). São Paulo, Brazil
  • 5. Instituto de Microbiologia Paulo de Góes Universidade Federal do Rio de Janeiro. Rio de Janeiro, Brazil.
  • 6. D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.
  • 7. D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil
  • 8. Clementino Fraga University Hospital, Federal University of Rio de Janeiro. Rio de Janeiro, Brazil
  • 9. National Center for Structural Biology and Bioimaging, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
  • 10. Department of Computing Science. Federal University of Ceará. Ceara, Brazil
  • 11. Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, São Paulo, Brazil
  • 12. Department of Bioengineering, School of Engineering, University of California, Merced, CA. USA

Description

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia. Several conditions sensitize to AF, most of which involve inflammation. Here we show sustained, low levels of IL-1β, suffice to sensitize to AF. We found low grade systemic inflammation in mice 15 days after the onset of IL-1b injections, a pattern like that found in AF patients. IL-1β increased caspase-1 maturation in left atria (LA), in a positive feedback loop. Injections of IL-1β in mice shortened action potential (AP), produced a faster restitution of both AP and Ca2+ transient. In addition, an increased fibrosis and enriched β-pleated proteins was found in LA. IL-1β injections sensitized to LA triggered activity (TA) and to AF. Prolongation of AP and the lack of caspase-1 or IL-1R inhibited sensitization to TA. Caspase-1 and IL-1R knockout mice could not be sensitized to AF by IL-1β injections, indicating it depends on IL-1R and caspase-1 expression. We propose a new model of pacing-induced AF, solely elicited by a key immune molecule, IL-1β. Our findings reveal a mechanism of AF induction by IL-1β, offering several new therapeutical targets to be tested, particularly in conditions in which IL-1β and AF are associated, such as gout, diabetes mellitus, obesity, and hypertension.

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