DACT2 regulates structural and electrical atrial remodeling in atrial fibrillation.

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia. DACT2 is a novel and important mediator of signaling pathways. The aim of this study was to investigate the clinical significance and functions of DACT2 expression in AF. Methods: Immunohistochemistry was used to detect the DACT2 expression pattern in valvular disease patients. DACT2 was overexpressed in HL-1 cells and primary atrial fibroblasts. The expression levels of the potassium channel, the L-type calcium current channel, sodium ion channel proteins and collagen proteins were detected by real-time polymerase chain reaction (RT-PCR). The proteins involved in the Wnt and TGF-beta signaling pathways were detected after DACT2 overexpression by western blotting. Results: DACT2 expression was significantly associated with AF (P=0.016). The fibrosis ratio in the strong DACT2 expression group was significantly lower than that in the weak DACT2 expression group (weak: 0.198 +/- 0.091, strong: 0.129 +/- 0.064, P=0.048), and a negative correlation between DACT2 expression levels and fibrosis severity was observed (Spearman rho =-0.476, P=0.010). DACT2 significantly increased the expression levels of KCNE5 and decreased the levels of KCNH2 and SCN5A. Overexpression of DACT2 significantly inhibited the expression of collagen I and collagen III in primary rat atrial fibroblasts. DACT2 could facilitate beta-catenin accumulation by reducing its phosphorylation at Thr41/Ser45 in ILL-1 cells and inhibit the TGF-beta signaling pathway in primary atrial fibroblasts. Conclusions: DACT2 played a role in AF by regulating both structural and electrical atrial remodeling and by affecting beta-catenin accumulation and TGF-beta signaling, and it could serve as a protective factor against AF in valvular heart disease.