Arrhythmias & electrophysiology
Atrial cardiomyocyte-restricted cleavage of gasdermin D promotes atrial arrhythmogenesis
Authors' conclusion
These findings establish a unique pyroptosis-independent role of NT-GSDMD in ACMs and arrhythmogenesis, which involves ROS-driven mitochondrial dysfunction.
Study context
- Population
- Atrial cardiomyocytes from human atrial appendages of atrial fibrillation (AF) patients and mice
- Comparison
- ACM-restricted NT-GSDMD overexpression vs control
- Outcome
- Function of NT-GSDMD in ACMs and its contribution to atrial arrhythmogenesis
Methodological detailshuman atrial appendage tissue, mouse model
- Human atrial appendage tissue
- Mouse model
Main finding
As reported in the abstract
NT-GSDMD in ACMs and atrial arrhythmogenesis
- Gasdermin D (GSDMD) cleavage enhanced in atrial cardiomyocytes (ACMs) of AF patients
- ACM-restricted NT-GSDMD overexpression increased susceptibility to pacing-induced AF
- NT-GSDMD pore formation facilitated interleukin-1β secretion from ACMs, promoting macrophage infiltration
- Up-regulated ESCRT-mediated membrane repair prevented pyroptosis in ACMs
- NT-GSDMD directly targeted mitochondria, increasing mitochondrial reactive oxygen species (ROS) generation, triggering proarrhythmic calcium-release events
- NT-GSDMD-induced arrhythmogenesis mitigated by mitochondrial-specific antioxidant MitoTEMPO
- Mutant NT-GSDMD lacking pore formation failed to cause mitochondrial dysfunction or induce atrial arrhythmia
- Genetic ablation of Gsdmd prevented spontaneous AF development in a mouse model
Original publication
Atrial cardiomyocyte-restricted cleavage of gasdermin D promotes atrial arrhythmogenesis. Eur Heart J. Published 10 February 2025. doi:10.
Summarised from the published abstract; every number is checked against it