Decreased Left Atrial Cardiomyocyte FGF13 Expression Increases Vulnerability to Postoperative Atrial Fibrillation in Humans.
Matthew A FischerAdrian ArrietaMarina AngeliniElizabeth SoehalimDouglas J ChapskiRichard J SheminThomas M VondriskaRiccardo OlcesePublished in: bioRxiv : the preprint server for biology (2024)
Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery and a significant cause of increased morbidity and mortality. The development of novel POAF therapeutics has been limited by an insufficient understanding of molecular mechanisms promoting atrial fibrillation. In this observational cohort study, we enrolled 28 patients without a history of atrial fibrillation that underwent mitral valve surgery for degenerative mitral regurgitation and obtained left atrial tissue samples along the standard atriotomy incision in proximity to the right pulmonary veins. We isolated cardiomyocytes and performed transcriptome analyses demonstrating 13 differentially expressed genes associated with new-onset POAF. Notably, decreased expression of fibroblast growth factor 13 (FGF13), a fibroblast growth factor homologous factor known to modulate voltage-gated sodium channel Na V 1.5 inactivation, had the most significant association with POAF. To assess the functional significance of decreased FGF13 expression in atrial myocytes, we performed patch clamp experiments on neonatal rat atrial myocytes after siRNA-mediated FGF13 knockdown, demonstrating action potential prolongation. These critical findings indicate that decreased FGF13 expression promotes vulnerability to POAF.
Keyphrases
- left atrial
- atrial fibrillation
- mitral valve
- catheter ablation
- poor prognosis
- left ventricular
- oral anticoagulants
- left atrial appendage
- direct oral anticoagulants
- heart failure
- newly diagnosed
- patients undergoing
- binding protein
- ejection fraction
- pulmonary hypertension
- percutaneous coronary intervention
- end stage renal disease
- coronary artery bypass
- drug delivery
- dna repair
- oxidative stress
- venous thromboembolism
- small molecule
- human health
- endothelial cells
- risk assessment
- cancer therapy
- laparoscopic surgery
- patient reported