Abstract
Epicardial adipose tissue (EAT) remodelling is closely related to the pathogenesis of atrial fibrillation (AF). We investigated whether metformin (MET) prevents AF‐dependent EAT remodelling and AF vulnerability in dogs. A canine AF model was developed by 6‐week rapid atrial pacing (RAP), and electrophysiological parameters were measured. Effective refractory periods (ERP) were decreased in the left and right atrial appendages as well as in the left atrium (LA) and right atrium (RA). MET attenuated the RAP‐induced increase in ERP dispersion, cumulative window of vulnerability, AF inducibility and AF duration. RAP increased reactive oxygen species (ROS) production and nuclear factor kappa‐B (NF‐κB) phosphorylation; up‐regulated interleukin‐6 (IL‐6), tumour necrosis factor‐α (TNF‐α) and transforming growth factor‐β1 (TGF‐β1) levels in LA and EAT; decreased peroxisome proliferator‐activated receptor gamma (PPARγ) and adiponectin (APN) expression in EAT and was accompanied by atrial fibrosis and adipose infiltration. MET reversed these alterations. In vitro, lipopolysaccharide (LPS) exposure increased IL‐6, TNF‐α and TGF‐β1 expression and decreased PPARγ/APN expression in 3T3‐L1 adipocytes, which were all reversed after MET administration. Indirect coculture of HL‐1 cells with LPS‐stimulated 3T3‐L1 conditioned medium (CM) significantly increased IL‐6, TNF‐α and TGF‐β1 expression and decreased SERCA2a and p‐PLN expression, while LPS + MET CM and APN treatment alleviated the inflammatory response and sarcoplasmic reticulum Ca2+ handling dysfunction. MET attenuated the RAP‐induced increase in AF vulnerability, remodelling of atria and EAT adipokines production profiles. APN may play a key role in the prevention of AF‐dependent EAT remodelling and AF vulnerability by MET.
Highlights
Atrial fibrillation (AF), the most common arrhythmia, is associated with increased morbidity and mortality.[1]
Inflammation is a known contributor to AF, it is difficult to elucidate the anti-inflammatory effects of AF therapy
After 6-week rapid atrial pacing (RAP), there was a significant increase in ∑window of vulnerability (WOV) compared to sham-operated group (201.7 ± 51.5 vs 46.7 ± 15.1 ms, P < .01), which was attenuated by MET WOV (201.7 ± 51.5 to 101.7 ± 31.9 ms, P < .001) (Figure 1C)
Summary
Atrial fibrillation (AF), the most common arrhythmia, is associated with increased morbidity and mortality.[1]. The important role of EAT in AF genesis and perpetuation has been investigated.[2,3] EAT may lead to AF via atrial structural and electrical remodelling via various mechanisms.[4] EAT infiltration alters the atrial electrophysiological properties, while various adipokines secreted by EAT influence AF pathogenesis. In the disease state, such as AF, the EAT secretome profile is remodelled This is characterized by a decrease in the release of homeostatic protective factors and an increase in the release of pathological adipokines.[4,5] These activities promote atrial inflammation and lead to structural and electrical remodelling.[6,7] inflammation is a known contributor to AF, it is difficult to elucidate the anti-inflammatory effects of AF therapy. The aims of this study were as follows: (a) to determine the impact of AF on EAT remodelling and the role of AF-dependent EAT remodelling in atrial fibrosis and AF maintenance; (b) to evaluate whether MET reverses AF-dependent EAT remodelling
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
