IL-1β sensitization to atrial fibrillation depends on caspase-1 expression
Creators
- Oscar Moreno-Loaiza1
- Narendra Vera-Nuñez1
- Ainhoa Rodriguez de Yurre Guirao1
- Manuela de Assumpção-Souza1
- Tatiana Pereira da Silva1
- Vinicius Cardoso Soares2
- Suelen Silva Gomes Dias2
- Leonardo Maciel1
- Humberto Muzi1
- Dahienne Ferreira de Oliveira1
- Bruno Cabral Braga1
- Luan Pereira Diniz3
- Mario Costa Cruz4
- Archimedes Barbosa Castro-Junior1
- Luciana Conde1
- Mauro Jorge Cabral-Castro5
- Olga Ferreira de Souza6
- Martha Valéria Tavares Pinheiro6
- Nilson Araújo de Oliveira Junior6
- Leonardo Rezende de Siqueira6
- Rodrigo Periquito Cosenza6
- Claudio Munhoz da Fontoura6
- Jose Carlos Pizzolante Secco6
- Juliana da Rocha Ferreira6
- Andréa Silvestre de Sousa6
- Denilson Albuquerque7
- Ronir Raggio Luiz6
- Isalira Peroba Ramos8
- Fernando A. Bozza6
- João Paulo do Vale Madeiro9
- Roberto Coury Pedrosa7
- Marcela Sorelli Carneiro-Ramos10
- Herculano da Silva Martinho10
- Patrícia T. Bozza2
- Renata Moll-Bernardes6
- Claudia Neto Paiva8
- Ariel L. Escobar11
- Emiliano Medei1
- 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. Clementino Fraga University Hospital, Federal University of Rio de Janeiro. Rio de Janeiro, Brazil
- 8. National Center for Structural Biology and Bioimaging, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- 9. Department of Computing Science. Federal University of Ceará. Ceara, Brazil
- 10. Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, São Paulo, Brazil
- 11. 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.
Files
routine_FTIR_spectra_analysis.txt
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(6.5 kB)
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