| Author | Moreno-Loaiza, Oscar | |
| Author | Soares, Vinicius Cardoso | |
| Author | Souza, Manuela de Assumpção | |
| Author | Vera-Nuñez, Narendra | |
| Author | Guirao, Ainhoa Rodriguez de Yurre | |
| Author | Silva, Tatiana Pereira da | |
| Author | Pozes, Ana Beatriz | |
| Author | Perticarrari, Larissa | |
| Author | Monteiro, Evelin | |
| Author | Albino, Maria Clara | |
| Author | Silva, Sophia Barros | |
| Author | Dias, Suelen Silva Gomes | |
| Author | Maciel, Leonardo | |
| Author | Muzi-Filho, Humberto | |
| Author | Oliveira, Dahienne Ferreira de | |
| Author | Braga, Bruno Cabral | |
| Author | Diniz, Luan Pereira | |
| Author | Cruz, Mario Costa | |
| Author | Barbosa, Simone Reis | |
| Author | Castro-Junior, Archimedes Barbosa | |
| Author | Conde, Luciana | |
| Author | Cabral-Castro, Mauro Jorge | |
| Author | Souza, Olga Ferreira de | |
| Author | Pinheiro, Martha Valéria Tavares | |
| Author | Oliveira Junior, Nilson Araújo de | |
| Author | Siqueira, Leonardo Rezende de | |
| Author | Cosenza, Rodrigo Periquito | |
| Author | Fontoura, Claudio Munhoz da | |
| Author | Secco, Jose Carlos Pizzolante | |
| Author | Ferreira, Juliana da Rocha | |
| Author | Sousa, Andréa Silvestre de | |
| Author | Albuquerque, Denilson | |
| Author | Luiz, Ronir Raggio | |
| Author | Nicolau-Neto, Pedro | |
| Author | Pretti, Marco Antonio | |
| Author | Boroni, Mariana | |
| Author | Bonamino, Martin Hernán | |
| Author | Kasai-Brunswick, Tais Hanae | |
| Author | Mello, Debora Bastos | |
| Author | Gonçalves-Silva, Triciana | |
| Author | Peroba, Isalira | |
| Author | Bozza, Fernando Augusto | |
| Author | Madeiro, João Paulo do Vale | |
| Author | Pedrosa, Roberto Coury | |
| Author | Carneiro-Ramos, Marcela Sorelli | |
| Author | Martinho, Herculano da Silva | |
| Author | Bozza, Patrícia Torres | |
| Author | Souza, Fernanda Mesquita de | |
| Author | Silva, Gabriel Victor Lucena da | |
| Author | Cunha, Thiago M. | |
| Author | Uzelac, Ilija | |
| Author | Fenton, Flavio | |
| Author | Moll-Bernardes, Renata | |
| Author | Paiva, Claudia N. | |
| Author | Escobar, Ariel L. | |
| Author | Medei, Emiliano | |
| Access date | 2025-04-22T23:11:53Z | |
| Available date | 2025-04-22T23:11:53Z | |
| Document date | 2025 | |
| Citation | MORENO-LOAIZA, Oscar et al. IL-1β enhances susceptibility to atrial fibrillation in mice by acting through resident macrophages and promoting caspase-1 expression. Nature Cardiovascular Research, v. 4, n. 3, p. 1-50, Mar. 2025. | en_US |
| ISSN | 2731-0590 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/69798 | |
| Sponsorship | This work was funded by Carlos Chagas Filho Foundation for Supporting Research in the State of Rio de Janeiro (FAPERJ) E26/200.396/2020, 200.067/2024 (to O.M.L.), Fundação Maria Emilia (to O.M.L.) and E.M. receives personal grant PQ CNPq, and grants E-26/210.155/2020, E-26/203.169/2017, E-6/210.191/2020, E-26/210.253/2020, E-203913/2024; E-210040/2023; CNPq 310681/2018–9, 308097/2022–0, and 406761/2022–1 INTERAS – INCT. F.F. receives personal grant 2R01HL 143450–05A1. The authors thank Dra. Alicia Mattiazzi - Centro de Investigaciones Cardiovasculares - Universidad Nacional de La Plata- for the critical discussion regarding the manuscript revision. The authors thank the FACS facility and Luminex facility from the Rede de Plataformas Tecnológicas FIOCRUZ. V.C.S. receives personal grant Program of Immunology and Inflammation, Federal University of Rio de Janeiro. P.T.B. receives personal grant FAPERJ E26/203.983/2024; E26/210.617/2023 and CNPq 442211/2024–4. | en_US |
| Language | eng | en_US |
| Publisher | Springer Nature | en_US |
| Rights | open access | en_US |
| Title | IL-1β enhances susceptibility to atrial fibrillation in mice by acting through resident macrophages and promoting caspase-1 expression | en_US |
| Type | Article | en_US |
| DOI | 10.1038/s44161-025-00610-8 | |
| Abstract | Atrial fibrillation (AF) is more prevalent in patients with elevated interleukin (IL)-1β levels. Here we show that daily administration of IL-1β for 15 days sensitizes mice to AF, leading to fibrosis, accumulation of β-pleated sheet proteins in the left atrium, and systemic inflammation, resembling the pathophysiological changes observed in patients with AF. IL-1β administration creates a positive feedback loop, dependent on the IL-1 receptor (IL-1R) activity in cardiac resident macrophages. This results in increased caspase-1 maturation in the left atrium and elevated Il1b and Casp1 transcription in atrial macrophages. IL-1β treatment accelerated action potential and Ca2+ restitution in the left atrium, leading to action-potential shortening. This, along with increased caspase-1 maturation and IL-1R signaling, was essential for inducing AF. Lack of IL-1R in macrophages, but not cardiomyocytes, prevented IL-1β-induced AF sensitivity. By depleting recruited macrophages or deleting IL-1R specifically in cardiac resident macrophages, we further demonstrate that IL-1β/IL-1R signaling in these resident macrophages is responsible for increased AF susceptibility. These findings offer insights into the therapeutic potential of targeting IL-1β/IL-1R signaling in patients with AF and emphasize the importance of recognizing different underlying causes in this patient group. | en_US |
| Affilliation | Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil / D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Oswaldo Cruz Foundation. Oswaldo Cruz Institute. Laboratory of Immunopharmacology. Rio de Janeiro, RJ, Brazil / Oswaldo Cruz Foundation. Oswaldo Cruz Institute. Center for Research, Innovation and Surveillance in COVID-19 and Heath Emergencies. Rio de Janeiro, RJ, Brazil / Federal University of Rio de Janeiro. Program of Immunology and Inflammation. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Oswaldo Cruz Foundation. Oswaldo Cruz Institute. Laboratory of Immunopharmacology. Rio de Janeiro, RJ, Brazil / Oswaldo Cruz Foundation. Oswaldo Cruz Institute. Center for Research, Innovation and Surveillance in COVID-19 and Heath Emergencies. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Federal University of Rio de Janeiro. Institute of Medical Biochemistry Leopoldo de Meis. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Federal University of Rio de Janeiro. Institute of Biomedical Sciences. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Universidade de São Paulo. Centro de Facilidades e Apoio à Pesquisa. São Paulo, SP, Brasil. | en_US |
| Affilliation | D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil / Fluminense Federal University. Pathology Department. Niterói, RJ, Brazil. | en_US |
| Affilliation | D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Rio de Janeiro State University. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Federal University of Rio de Janeiro. Institute for Studies in Public Health. Rio de Janeiro, RJ, Brazil / Federal University of Rio de Janeiro. Clementino Fraga University Hospital. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Brazilian National Cancer Institute. Research Coordination. Molecular Carcinogenesis Program. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | National Cancer Institute. Research Coordination. Cell and Gene Therapy Program. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Brazilian National Cancer Institute. Division of Experimental and Translational Research. Laboratory of Bioinformatics and Computational Biology. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Brazilian National Cancer Institute. Research Coordination. Molecular Carcinogenesis Program. Rio de Janeiro, RJ, Brazil / Oswaldo Cruz Foundation. Vice-Presidency of Research and Biological Collections. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil / Federal University of Rio de Janeiro. National Center for Structural Biology and Bioimaging. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Federal University of Rio de Janeiro. National Center for Structural Biology and Bioimaging. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Federal University of Rio de Janeiro. National Center for Structural Biology and Bioimaging. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Federal University of Rio de Janeiro. National Center for Structural Biology and Bioimaging. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Medicina Intensiva. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Federal University of Ceará. Department of Computing Science. Fortaleza, CE, Brazil. | en_US |
| Affilliation | Federal University of Rio de Janeiro. Clementino Fraga University Hospital. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Federal University of ABC. Center for Natural and Human Sciences. Santo André, SP, Brazil. | en_US |
| Affilliation | Federal University of ABC. Center for Natural and Human Sciences. Santo André, SP, Brazil. | en_US |
| Affilliation | Oswaldo Cruz Foundation. Oswaldo Cruz Institute. Laboratory of Immunopharmacology. Rio de Janeiro, RJ, Brazil / Oswaldo Cruz Foundation. Oswaldo Cruz Institute. Center for Research, Innovation and Surveillance in COVID-19 and Heath Emergencies. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | University of Sao Paulo. Ribeirão Preto Medical School. Center of Research in Inflammatory Diseases. Ribeirao Preto, SP, Brazil / University of Sao Paulo. Ribeirao Preto Medical School. Department of Pharmacology. Ribeirao Preto, SP, Brazil. | en_US |
| Affilliation | Federal University of ABC. Center for Natural and Human Sciences. Santo André, SP, Brazil / University of Sao Paulo. Ribeirão Preto Medical School. Center of Research in Inflammatory Diseases. Ribeirao Preto, SP, Brazil. | en_US |
| Affilliation | University of Sao Paulo. Ribeirão Preto Medical School. Center of Research in Inflammatory Diseases. Ribeirao Preto, SP, Brazil / University of Sao Paulo. Ribeirao Preto Medical School. Department of Pharmacology. Ribeirao Preto, SP, Brazil. | en_US |
| Affilliation | Virginia Commonwealth University. Richmond, VA, USA. | en_US |
| Affilliation | School of Physics. Georgia Tech. Atlanta, GA, USA. | en_US |
| Affilliation | D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | University of California. School of Engineering. Department of Bioengineering. Merced, CA, USA. | en_US |
| Affilliation | Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil / D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / Federal University of Rio de Janeiro. National Center for Structural Biology and Bioimaging. Rio de Janeiro, RJ, Brazil. | en_US |
| Subject | Atrial fibrillation | en_US |
| Subject | Interleukin-1β | en_US |
| Subject | Inflammation | en_US |
| Subject | Caspase-1 | en_US |
| Subject | Arrhythmia | en_US |
| e-ISSN | 2731-0590 | |
