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DACT1 Involvement in the Cytoskeletal Arrangement of Cardiomyocytes in Atrial Fibrillation by Regulating Cx43.

Authors
  • Hou, Jian1, 2
  • Yue, Yuan1, 2
  • Hu, Bo3
  • Xu, Guangtao3
  • Su, Ruibing4
  • Lv, Linhua1
  • Huang, Jiaxing1
  • Yao, Jianping1
  • Guan, Yuanjun5
  • Wang, Keke1, 2
  • Wu, Zhongkai1, 2
  • 1 The First Affiliated Hospital of Sun Yat-Sen University Department of Cardiac Surgery Guangzhou GD People's Republic of China Department of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, GD, People's Republic of China. , (China)
  • 2 Sun Yat-Sen University NHC Key Laboratory of Assisted Circulation Guangzhou GD People's Republic of China NHC Key Laboratory of Assisted Circulation, Sun Yat-Sen University, Guangzhou, GD, People's Republic of China. , (China)
  • 3 Jiaxing University Jiaxing Hospital of Traditional Chinese Medicine Department of Pathology and Molecular Medicine Center Jiaxing ZJ People's Republic of China Department of Pathology and Molecular Medicine Center, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing University, Jiaxing, ZJ, People's Republic of China. , (China)
  • 4 Shantou University Medical College Department of Forensic Pathology Shantou GD People's Republic of China Department of Forensic Pathology, Shantou University Medical College, Shantou, GD, People's Republic of China. , (China)
  • 5 Sun Yat-Sen University Zhongshan School of Medicine Core Lab Plat for Medical Science Guangzhou GD People's Republic of China Core Lab Plat for Medical Science, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, GD, People's Republic of China. , (China)
Type
Published Article
Journal
Brazilian journal of cardiovascular surgery
Publication Date
Jan 01, 2020
Volume
34
Issue
6
Pages
711–722
Identifiers
DOI: 10.21470/1678-9741-2019-0033
PMID: 31545578
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

To determine the role of the dishevelled binding antagonist of beta catenin 1 (DACT1) in the cytoskeletal arrangement of cardiomyocytes in atrial fibrillation (AF). The DACT1 expression and its associations with the degree of fibrosis and β-catenin in valvular disease patients were analyzed by immunohistochemistry and Masson's staining. DACT1 was overexpressed in the atrial myocyte cell line (HL-1) and the cardiac cell line (H9C2) by adenoviral vectors. Alterations in the fibrous actin (F-actin) content and organization and the expression of β-catenin were detected by flow cytometry, immunofluorescence, and Western blotting. Additionally, the association of DACT1 with gap junctions connexin 43 (Cx43) was detected by immunohistochemistry, immunofluorescence, and Western blotting. Decreased cytoplasmic DACT1 expression in the myocardium was associated with AF (P=0.037) and a high degree of fibrosis (weak vs. strong, P=0.028; weak vs. very strong, P=0.029). A positive association was observed between DACT1 and β-catenin expression in clinical samples (P=0.028, Spearman's rho=0.408). Furthermore, overexpression of DACT1 in HL-1 and H9C2 cells induced an increase in β-catenin and subsequent partial colocalization of DACT1 and β-catenin. In addition, F-actin content and organization were enhanced. Interestingly, DACT1 was positively correlated with the Cx43 expression in clinical samples (P=0.048, Spearman's rho=0.370) and changed the Cx43 distribution in cardiac cell lines. DACT1 proved to be a novel AF-related gene by regulating Cx43 via cytoskeletal organization induced by β-catenin accumulation in cardiomyocytes. DACT1 could thus serve as a potential therapeutic marker for AF.

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