Arrhythmias & electrophysiologyMechanistic study
Decreased METTL3 in atrial myocytes promotes atrial fibrillation
- Mechanistic study
Authors' conclusion
Our study established the pathophysiological role of METTL3 involved in the development of AF
Study context
- Population
- Patients with persistent atrial fibrillation (AF) (left atrial appendages) and experimental AF mouse models (cAMP-responsive element modulator (CREM) transgenic and CaCl2-ACh-injected mice)
Main finding
As reported in the abstract
METTL3 expression and its role in AF (mechanistic)
- METTL3 protein and RNA m6A modification levels significantly reduced in left atrial appendages (LAAs) of patients with AF and experimental AF models
- Genetic inhibition of METTL3 promoted AF development in CREM transgenic mice and CaCl2-ACh-injected mice
- METTL3 knockdown in atrial myocytes enhanced calcium handling
- Reduced METTL3 increased SR Ca2+-ATPase Type 2a activity by up-regulating protocadherin gamma subfamily A, 10
- Decreased METTL3 in atrial myocytes attributed to down-regulation of the cAMP-responsive element-binding protein 1/ubiquitin-specific peptidase 9 X-linked axis
Original publication
Decreased METTL3 in atrial myocytes promotes atrial fibrillation. Europace. Published 24 February 2025. doi:10.1093/europace/euaf021
Summarised from the published abstract; every number is checked against it