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Fibroblast-Restricted Inflammasome Activation Promotes Atrial Fibrillation and Heart Failure With Diastolic
Luge Li1, Cristian Coarfa2, Yue Yuan1
1Department of Medicine (Section of Cardiovascular Research), Baylor College of Medicine, Houston, Texas, USA.
JACC. Basic to Translational Science
|April 17, 2025
Summary
The NLR family pyrin domain containing 3 (NLRP3) inflammasome in atrial fibroblasts promotes atrial fibrillation (AF) and heart failure by increasing fibrosis and reducing conduction velocity. Inhibiting NLRP3 in fibroblasts may prevent AF-related heart disease.
Area of Science:
- Cardiology
- Immunology
- Fibrosis Research
Background:
- Atrial fibrillation (AF) and heart failure frequently coexist.
- Both conditions involve inflammatory signaling and cardiac fibroblasts.
- The role of fibroblast inflammasomes in AF and heart failure is not fully understood.
Purpose of the Study:
- To investigate the role of the NLR family pyrin domain containing 3 (NLRP3) inflammasome in cardiac fibroblasts.
- To determine the impact of fibroblast NLRP3 activation on atrial function and heart failure.
Main Methods:
- NLRP3 expression was analyzed in atrial fibroblasts from AF patients.
- Fibroblast-specific NLRP3 activation was induced in mice.
- Cardiac function, fibrosis, and conduction velocity were assessed.
- NLRP3 knockdown was performed to evaluate its protective effects.
Main Results:
- NLRP3 was upregulated in atrial fibroblasts from AF patients.
- Fibroblast-specific NLRP3 activation in mice led to AF-promoting atrial myopathy and diastolic dysfunction.
- Increased fibrosis and reduced conduction velocity were observed.
- NLRP3 knockdown mitigated AF-promoting atrial substrate and cardiomyopathy.
Conclusions:
- The fibroblast NLRP3 inflammasome is a key pathway in promoting proarrhythmic fibrosis in AF.
- NLRP3 activation in fibroblasts contributes to cardiomyopathy and diastolic dysfunction.
- Targeting fibroblast NLRP3 may offer a therapeutic strategy for AF and heart failure.
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