Resveratrol prevents atrial fibrillation by inhibiting atrial structural and metabolic remodeling in collagen-induced arthritis rats

Rheumatoid arthritis (RA) causes atrial remodeling that induces the occurrence and maintenance of atrial fibrillation (AF). In this study, we explored the influence of RA on atrial fibrillation and the potential therapeutic effects of resveratrol in a rat model. The following three groups of female Wistar rats (8 weeks old) were used in this study: control, collagen-induced arthritis (CIA), and resveratrol. Rats in the CIA and resveratrol groups were injected twice with type II collagen in Freund’s incomplete adjuvant. Three weeks after the second injection, resveratrol (10 mg kg−1 day−1) was administered for 4 weeks. Subsequently, atrial electrophysiological parameters were measured. Levels of inflammatory factors in the atria and serum were measured. Atrial histopathological changes were assessed using microscopy, and cardiomyocyte apoptosis and fibrosis were assessed using TUNEL and Masson’s staining. Apoptosis-related and fibrosis-related proteins were assessed using Western blotting. Atrial adenosine triphosphate (ATP) and free fatty acid (FFA) levels were tested using ELISA. Glycogen accumulation and metabolism-related protein expression were assessed. AF inducibility and duration were markedly increased in CIA rats and were reduced by resveratrol. CIA also increased the atrial and serum IL-6 and TNF-a levels and induced atrial apoptosis and fibrosis, which were attenuated by resveratrol. Moreover, CIA induced the impairment of atrial energy metabolism by inhibiting the AMPK/PGC-1α pathway, which was reversed by resveratrol. Resveratrol protects against RA-induced atrial structural and metabolic remodeling, which may provide a new potential therapeutic treatment for RA-related AF.