ArticleEuropean heart journal2025
Atrial cardiomyocyte-restricted cleavage of gasdermin D promotes atrial arrhythmogenesis.
Article in European heart journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- The Immune System as a Proarrhythmic Mediator: A Novel Paradigm for the Development of New Antiarrhythmic Therapy.The Canadian journal of cardiology · 2026Review
- Gut microbiota-atrium axis: Microbiota metabolite-mediated regulation of the NLRP3 inflammasome in atrial fibrillation-pathophysiological roles and therapeutic perspectives.Heart rhythm O2 · 2026Review
- The clinical pathophysiology of atrial fibrillation: outstanding questions from bedside to bench and back.Physiological reviews · 2026Review
- Seawater Immersion Hypothermia Triggers Cardiac Pyroptosis via the NF-κB/NLRP3 Inflammasome Axis: A Mechanistic Study in Rats.International journal of molecular sciences · 2026Article
- Identification of diagnostic and therapeutic roles of programmed cell death-related proteins in dilated cardiomyopathy: a multi-omics and experimental validation study.Scientific reports · 2026Article
- G protein-coupled receptors and inflammation resolution signaling networks in the heart: Pharmacology and potential for innovative therapeutics.Pharmacological reviews · 2026Review
- Joint assessment of insulin resistance surrogate indices and basal metabolic rate for primary prevention of cardiometabolic multimorbidity: evidence from the China Health and Retirement Longitudinal Study (2011-2020).Cardiovascular diabetology · 2026Article
- Impairment of mitochondrial quality control exacerbates diabetes-related atrial fibrillation by cGAS-STING signaling pathway and cardiomyocyte-macrophage crosstalk.Theranostics · 2026Article
- Inflammasome-associated pyroptosis and tumor angiogenesis in prostate cancer.Iranian journal of basic medical sciences · 2026Review
- Targeted nanodelivery strategies for atrial fibrillation: concomitant targeting of fibrosis suppression and electrical conduction restoration through advanced nanobiotechnology.Journal of nanobiotechnology · 2025Review
- Amorphous layered double hydroxide-based nano-enzyme eye drops against dry eye disease by inhibiting mitochondrial damage and pyroptosis.Journal of nanobiotechnology · 2025Article
- Mineralocorticoid Receptor Antagonism Reduces Atrial Arrhythmias Post-Cardiac Surgery and Attenuates Atrial Stress Responses to Cardioplegic Arrest.Journal of the American Heart Association · 2025Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
BACKGROUND AND
aimsEnhanced inflammatory signalling causally contributes to atrial fibrillation (AF) development. Gasdermin D (GSDMD) is an important downstream effector of several inflammasome pathways. However, the role of GSDMD, particularly the cleaved N-terminal (NT)-GSDMD, in non-immune cells remains elusive. This study aimed to elucidate the function of NT-GSDMD in atrial cardiomyocytes (ACMs) and determine its contribution to atrial arrhythmogenesis.
methodsHuman atrial appendages were used to assess the protein levels and localization. A modified adeno-associated virus 9 was employed to establish ACM-restricted overexpression of NT-GSDMD in mice.
resultsThe cleavage of GSDMD was enhanced in ACMs of AF patients. Atrial cardiomyocyte-restricted overexpression of NT-GSDMD in mice increased susceptibility to pacing-induced AF. The NT-GSDMD pore formation facilitated interleukin-1β secretion from ACMs, promoting macrophage infiltration, while up-regulating 'endosomal sorting complexes required for transport'-mediated membrane-repair mechanisms, which prevented inflammatory cell death (pyroptosis) in ACMs. Up-regulated NT-GSDMD directly targeted mitochondria, increasing mitochondrial reactive oxygen species (ROS) generation, which triggered proarrhythmic calcium-release events. The NT-GSDMD-induced arrhythmogenesis was mitigated by the mitochondrial-specific antioxidant MitoTEMPO. A mutant NT-GSDMD lacking pore-formation capability failed to cause mitochondrial dysfunction or induce atrial arrhythmia. Genetic ablation of Gsdmd prevented spontaneous AF development in a mouse model.
conclusionsThese findings establish a unique pyroptosis-independent role of NT-GSDMD in ACMs and arrhythmogenesis, which involves ROS-driven mitochondrial dysfunction. Mitochondrial-targeted therapy, either by reducing ROS production or inhibition of GSDMD, prevents AF inducibility, positioning GSDMD as a novel therapeutic target for AF prevention.
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