Key result
c-Ski overexpression reduces AF inducibility, duration, and atrial fibrosis in a rapid pacing model.
Why the study?
Atrial fibrosis contributes to the initiation and maintenance of AF, making its pathogenesis a potential source of therapeutic targets.
Does c-Ski overexpression reduce atrial remodeling and atrial fibrillation inducibility in a rapid atrial pacing canine model?
Does c-Ski overexpression reduce atrial remodeling and atrial fibrillation inducibility in a rapid atrial pacing canine model?
c-Ski overexpression improves atrial remodeling and reduces atrial fibrillation vulnerability by suppressing TGF-β1-Smad and p38 MAPK pathways, suggesting a potential therapeutic target.
Hypothesis-generating for c-Ski in canine AF models; leaves open translation to human therapy.
Atrial fibrosis is an important factor in the initiation and maintenance of atrial fibrillation (AF); therefore, understanding the pathogenesis of atrial fibrosis may reveal promising therapeutic targets for AF. In this study, we successfully established a rapid atrial pacing canine model and found that the inducibility and duration of AF were significantly reduced by the overexpression of c-Ski, suggesting that this approach may have therapeutic effects. c-Ski was found to be down-regulated in the atrial tissues of the rapid atrial pacing canine model. We artificially up-regulated c-Ski expression with a c-Ski-overexpressing adenovirus. Haematoxylin and eosin, Masson's trichrome and picrosirius red staining showed that c-Ski overexpression alleviated atrial fibrosis. Furthermore, we found that the expression levels of collagen III and α-SMA were higher in the groups of dogs subjected to right-atrial pacing, and this increase was attenuated by c-Ski overexpression. In addition, c-Ski overexpression decreased the phosphorylation of smad2, smad3 and p38 MAPK (p38α and p38β) as well as the expression of TGF-β1 in atrial tissues, as shown by a comparison of the right-atrial pacing + c-Ski-overexpression group to the control group with right-atrial pacing only. These results suggest that c-Ski overexpression improves atrial remodelling in a rapid atrial pacing canine model by suppressing TGF-β1-Smad signalling and p38 MAPK activation.
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Wang et al. (2019) studied Rapid atrial pacing canine model of atrial fibrillation (n=18). c-Ski-overexpressing adenovirus (Adc-Ski) vs. Sham-operated, rapid atrial pacing control, and rapid atrial pacing injected with control adenovirus (AdNull) was evaluated on Inducibility and duration of atrial fibrillation and atrial fibrosis (p=<0.05). c-Ski overexpression significantly reduced the inducibility and duration of atrial fibrillation and alleviated atrial fibrosis in a rapid atrial pacing canine model (p<0.05).
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