Accumulated β-catenin is associated with human atrial fibrosis and atrial fibrillation.

Autor: Bai, Ying, Li, Rui, Hao, Jun-Feng, Chen, Lian-Wan, Liu, Si-Tong, Zhang, Xi-Lin, Lip, Gregory Y. H., Yang, Jin-Kui, Zou, Yi-Xi, Wang, Hao
Předmět:
Zdroj: Journal of Translational Medicine; 8/5/2024, Vol. 22 Issue 1, p1-14, 14p
Abstrakt: Background: Atrial fibrillation (AF) is associated with increased risk of stroke and mortality. It has been reported that the process of atrial fibrosis was regulated by β-catenin in rats with AF. However, pathophysiological mechanisms of this process in human with AF remain unclear. This study aims to investigate the possible mechanisms of β-catenin in participating in the atrial fibrosis using human right atrial appendage (hRAA) tissues. Methods: We compared the difference of β-catenin expression in hRAA tissues between the patients with AF and sinus rhythm (SR). The possible function of β-catenin in the development of AF was also explored in mice and primary cells. Results: Firstly, the space between the membrane of the gap junctions of cardiomyocytes was wider in the AF group. Secondly, the expression of the gap junction function related proteins, Connexin40 and Connexin43, was decreased, while the expression of β-catenin and its binding partner E-cadherin was increased in hRAA and cardiomyocytes of the AF group. Thirdly, β-catenin colocalized with E-cadherin on the plasma membrane of cardiomyocytes in the SR group, while they were dissociated and accumulated intracellularly in the AF group. Furthermore, the expression of glycogen synthase kinase 3β (GSK-3β) and Adenomatous Polyposis Coli (APC), which participated in the degradation of β-catenin, was decreased in hRAA tissues and cardiomyocytes of the AF group. Finally, the development of atrial fibrosis and AF were proved to be prevented after inhibiting β-catenin expression in the AF model mice. Conclusions: Based on human atrial pathological and molecular analyses, our findings provided evidence that β-catenin was associated with atrial fibrosis and AF progression. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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