Effect of c‐Ski on atrial remodelling in a rapid atrial pacing canine model

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...

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Bibliographic Details
Published in:Journal of cellular and molecular medicine 2020-01, Vol.24 (2), p.1795-1803
Main Authors: Wang, Juan, Han, Min, Han, Su‐xia, Zhi, Cuiju, Gao, Suli, Li, Yao
Format: Article
Language:English
Subjects:
Adenoviruses
Animals
Antibodies
atrial fibrillation
atrial fibrosis
Atrial Remodeling
Cardiac Pacing, Artificial
Collagen
Collagen (type III)
Cytokines
c‐Ski
Disease Models, Animal
Dogs
Electrophysiological Phenomena
extracellular matrix
Extracellular Matrix - metabolism
Fibrillation
Fibroblasts
Fibrosis
Heart Atria - physiopathology
Immunoglobulins
Infrared imaging systems
Laboratory animals
MAP kinase
Original
Ostomy
p38 MAPK
p38 Mitogen-Activated Protein Kinases - metabolism
Pathogenesis
Phosphorylation
Proteins
Proto-Oncogene Proteins - metabolism
Signal Transduction
Smad protein
Smad Proteins - metabolism
Smad2 protein
Smad3 protein
TGF‐β1/Smad signalling
Therapeutic applications
Transforming Growth Factor beta1 - metabolism
Transforming growth factor-b1
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Summary: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.
ISSN:1582-1838
1582-4934
DOI:10.1111/jcmm.14876