Resveratrol prevents atrial fibrillation by inhibiting atrial structural and metabolic remodeling in collagen-induced arthritis rats
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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.
KeywordsAtrial fibrillation Atrial remodeling Fibrosis Apoptosis Rheumatoid arthritis Resveratrol
AMP-activated protein kinase
Atrial effective refractory period
Bcl-2-associated X Protein
B cell lymphoma-2
Fatty acid translocase/cluster of differentiation 36
Free fatty acid
Glucose transporter 4
PPAR co-activator 1α
Tumor necrosis factor-α
Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling
Y. Z. and S. Z. designed and conducted the experiments, analyzed the data and wrote the manuscript. Y. Z., S. Z., Z. H. L., X. B. Z., Y. Y., and L. S. conducted the experiments. Y. L. designed the experiment and revised the manuscript. All authors approved the final version of the manuscript.
This work was financially supported by grants from the National Nature Scientific Foundation of China (no.81300133, no.81470462).
Compliance with ethical standards
All the protocols conformed to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (the 8th Edition, NRC 2011) and were approved by the Experimental Animals Ethics Committee in Harbin Medical University.
Conflicts of interest
The authors declare that they have no conflict of interest.
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