The worldwide incidence and prevalence of atrial fibrillation (AF) are increasing, making it a life-threatening condition due to the higher numbers of people suffering from obesity. Vaspin, an adipokine derived from epicardial adipose tissue, has been reported to reduce inflammation, inhibit apoptosis, and induce autophagy; however, its role in the pathogenesis of AF is not known. In this study, we investigated the role of vaspin in patients with AF and explored the molecular mechanisms using atrial myocytes in vitro . Our data showed that vaspin levels were significantly reduced in the plasma of patients with AF. Lower plasma levels of vaspin were also associated with a higher risk of AF in patients with obesity. Vaspin treatment in vitro alleviated cardiomyocyte injury, atrial fibrosis, atrial myocyte apoptosis, and mitochondrial injury in atrial myocytes following Ang-II stress. Moreover, our results demonstrated that vaspin protected against Ang-II-induced atrial myocyte dysfunction by inducing mitophagy. We also observed that vaspin treatment enhanced the phosphorylation of Fun14 domain-containing protein 1 (FUNDC1) at Ser17 by unc-51 like autophagy activating kinase 1 (ULK1), resulting in the induction of mitophagy. These positive effects of vaspin were reversed by ULK1 silencing in Ang-II-stimulated HL-1 cells. Our study is the first to propose that vaspin plays a vital role in AF pathogenesis via ULK1/FUNDC1-regulated mitophagy and could be a novel therapeutic target for AF.
Keyphrases
- atrial fibrillation
- catheter ablation
- oxidative stress
- left atrial
- oral anticoagulants
- left atrial appendage
- direct oral anticoagulants
- endoplasmic reticulum stress
- cell cycle arrest
- cell death
- adipose tissue
- angiotensin ii
- heart failure
- induced apoptosis
- insulin resistance
- percutaneous coronary intervention
- type diabetes
- diabetic rats
- metabolic syndrome
- risk factors
- weight loss
- transcription factor
- weight gain
- coronary artery disease
- endothelial cells
- nlrp inflammasome
- physical activity
- high fat diet induced
- high fat diet
- drug induced
- high resolution
- deep learning
- pi k akt
- left ventricular
- binding protein