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Published on: June 29, 2022
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Chronic kidney disease promotes atrial fibrillation via inflammasome pathway activation
Jia Song1, Jose Alberto Navarro-Garcia2,3, Jiao Wu4
1Department of Medicine (Cardiovascular Research).
The Journal of Clinical Investigation
|August 15, 2023
Summary
Chronic kidney disease (CKD) increases atrial fibrillation (AF) risk by activating the NLRP3 inflammasome in the atria. Inhibiting NLRP3 or IL-1β reduces AF incidence and atrial remodeling in CKD models.
Area of Science:
- Cardiology
- Nephrology
- Immunology
Background:
- Chronic kidney disease (CKD) elevates atrial fibrillation (AF) risk, but the underlying mechanisms are unclear.
- The NLRP3 inflammasome and its effector IL-1β are implicated in inflammation-related conditions like AF and CKD.
- Elevated IL-1β levels and enhanced NLRP3 activity are observed in CKD patients with AF.
Purpose of the Study:
- To investigate the role of NLRP3/IL-1β signaling in the development of AF in the context of CKD.
- To determine if targeting NLRP3 or IL-1β can mitigate CKD-induced AF.
Main Methods:
- A mouse model of CKD was established using a subtotal nephrectomy protocol.
- Mice were genetically modified (Nlrp3-/-) or treated with anti-IL-1β antibodies to inhibit NLRP3 inflammasome activation.
- Cardiac structure, electrophysiology, and AF susceptibility were assessed in CKD and control groups.
Main Results:
- CKD induced elevated serum and atrial IL-1β levels, increased AF susceptibility, and prolonged AF duration in wild-type mice.
- CKD mice exhibited abbreviated atrial effective refractory periods, enlarged atria, and atrial fibrosis.
- Genetic NLRP3 inhibition or anti-IL-1β antibody treatment normalized atrial dimensions, reduced fibrosis, and decreased AF incidence.
Conclusions:
- CKD promotes AF development through NLRP3 inflammasome activation in the atria, leading to structural and electrical remodeling.
- Targeting the NLRP3/IL-1β pathway, particularly with IL-1β neutralizing antibodies, shows therapeutic potential for preventing CKD-induced AF.
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