Vildagliptin alleviates cardiomyocyte apoptosis and inflammatory responses in the treatment of non-valvular atrial fibrillation by regulating the NO/sGC/cGMP signaling pathway.

AIM: to investigate the therapeutic effects of vildagliptin on non-valvular atrial fibrillation (NVAF) and to determine whether its underlying mechanism of action is associated with modulation of the nitric oxide/soluble guanylate cyclase/cyclic guanosine monophosphate (NO/sGC/cGMP) signaling pathway.

METHODS: Thirty clean-grade male Sprague-Dawley (SD) rats were enrolled. Atrial fibrillation was first induced by electrical stimulation of the vagus nerve. After confirming postoperative survival in all animals, the rats were randomly assigned to a normal control group (CG), an atrial fibrillation group (AFG), and a drug-treated group (DG), thereby establishing an NVAF rat model. Myocardial electro-physiological parameters, levels of inflammatory cytokines, the cardiomyocyte apoptosis index (AI), as well as nitric oxide (NO), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), and soluble guanylate cyclase (sGC) were measured and compared among the three groups.

RESULTS: Compared with the CG, the AFG exhibited significantly reduced effective refractory period (ERP), action potential duration at 90% repolarization (APD90), and the ERP/APD90 ratio, accompanied by markedly elevated levels of inflammatory cytokines and a higher AI. In addition, concentrations of NO, cAMP, and cGMP were significantly decreased, sGC expression was downregulated, and phosphodiesterase 5 A (PDE5A) expression was upregulated (all p < 0.05). In comparison with the AFG, rats in the DG showed significant increases in ERP, APD90, and the ERP/APD90 ratio, along with pronounced reductions in inflammatory cytokine levels and cardiomyocyte AI.

CONCLUSION: Vildagliptin can markedly improve the myocardial electrical and vascular functions and reduce cardiomyocyte apoptosis and inflammatory responses in NVAF.