Fibroblast-Restricted Inflammasome Activation Promotes Atrial Fibrillation and Heart Failure With Diastolic Dysfunction
Atrial fibrillation (AF) often coexists with heart failure, both involving inflammatory signaling and cardiac fibroblasts. To understand the role of fibroblast NLR family pyrin domain containing 3 (NLRP3) inflammasome in cardiac function, we found that NLRP3 was up-regulated in atrial fibroblasts from AF patients. Fibroblast-specific activation of NLRP3 in mice induced AF-promoting atrial myopathy and heart failure with diastolic dysfunction, accompanied by increased fibrosis, and reduced conduction velocity. Knockdown of NLRP3 prevented the AF-promoting atrial substrate and cardiomyopathy in the context of NLRP3 activation in fibroblasts. We identify the fibroblast NLRP3 inflammasome as a key pathway governing the promotion of proarrhythmic fibrosis in AF and cardiomyopathy.
Authors
- Jia Song (ORCID: https://orcid.org/0000-0002-0815-208X)
- Yuying Zeng
- Dobromir Dobrev (ORCID: https://orcid.org/0000-0002-4612-117X)
- Cristian Coarfa (ORCID: https://orcid.org/0000-0002-4183-4939)
- Lisa K. McClendon
- Sandra L. Grimm (ORCID: https://orcid.org/0000-0002-0682-3134)
- Markus Kamler (ORCID: https://orcid.org/0000-0001-6608-8496)
- Stanley Nattel (ORCID: https://orcid.org/0000-0002-5565-3311)
- Michelle D. Tallquist (ORCID: https://orcid.org/0000-0002-1383-144X)
- Luge Li (ORCID: https://orcid.org/0000-0002-4145-2607)
- Xiaolei Wang (ORCID: https://orcid.org/0009-0007-6808-5206)
- Issam Abu-Taha (ORCID: https://orcid.org/0000-0002-2298-8959)
- Na Li (ORCID: https://orcid.org/0000-0003-1307-3375)
- Yue Yuan (ORCID: https://orcid.org/0009-0003-3723-8178)
- Xiaohui Chen (ORCID: https://orcid.org/0000-0003-3723-513X)
- Amrit Koirala (ORCID: https://orcid.org/0009-0008-6323-6041)
Institutions
- University of Hawaii System (US)
- Université du Québec à Montréal (CA)
- Baylor College of Medicine (US)
- Montreal Heart Institute (CA)
- West German Heart and Vascular Center Essen (DE)
- University of Duisburg-Essen (DE)
Publication Details
- Journal
- JACC Basic to Translational Science
- Published
- 2025-04-16
- DOI
- https://doi.org/10.1016/j.jacbts.2025.02.004
- Citations
- 8
- Primary Topic
- Cardiovascular Disease and Adiposity
- Type
- article
- Field-Weighted Citation Impact
- 11.11
Funders
- American Heart Association
- National Heart, Lung, and Blood Institute