Dact1 involvement in the cytoskeletal arrangement of cardiomyocytes in atrial fibrillation by regulating cx43
Rev. bras. cir. cardiovasc
; 34(6): 711-722, Nov.-Dec. 2019. tab, graf
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| ID: biblio-1057503
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ABSTRACT
Abstract Objective:
To determine the role of the dishevelled binding antagonist of beta catenin 1 (DACT1) in the cytoskeletal arrangement of cardiomyocytes in atrial fibrillation (AF).Methods:
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.Results:
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.Conclusion:
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.
Texte intégral:
1
Indice:
LILACS
Sujet Principal:
Fibrillation auriculaire
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Cytosquelette
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Protéines nucléaires
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Connexine 43
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Myocytes cardiaques
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Protéines adaptatrices de la transduction du signal
Limites du sujet:
Adult
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Aged
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Female
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Humans
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Male
langue:
En
Texte intégral:
Rev. bras. cir. cardiovasc
Thème du journal:
CARDIOLOGIA
/
CIRURGIA GERAL
Année:
2019
Type:
Article