The transformation of atrial fibroblasts into myofibroblasts is promoted by trimethylamine N-oxide via the Wnt3a/beta-catenin signaling pathway

Background: Atrial fibrosis is an important pathophysiological mechanism in the development and maintenance of atrial fibrillation. Trimethylamine N-oxide (TMAO) is one of the most widely studied microbial metabolites involved in the promotion of cardiac fibrosis. TMAO promotes phenotypic transformation, proliferation, and migration and increases collagen secretion in cardiac fibroblasts. The Wnt/13-catenin pathway also plays a key role in the promotion of cardiac fibroblasts into myofibroblasts. Methods: The expression of Alpha-smooth muscle actin (a-SMA) was determined to identify the formation of myofibroblasts. The effects of TMAO on the proliferation and migration of atrial fibroblasts were detected by cell counting kit 8, and transwell assays, respectively. Western blot and immunofluorescence were used to detect the activation of the 13-catenin pathway by TMAO and the phenotypic transformation and collagen secretion of the atrial fibroblasts. Western blot and immunofluorescence assays were performed to detect the effects of exogenous Wnt3a and TMAO on the activation of 13-catenin pathway and the phenotypic transformation of atrial fibroblasts. Results: TMAO promoted the proliferation and migration of atrial fibroblasts. TMAO also promoted the phenotypic transformation, migration, and collagen secretion of the atrial fibroblasts by activating the 13-catenin pathway. Exogenous Wnt3a and TMAO synergistically promoted the activation and phenotypic transformation of the 13-catenin pathway in atrial fibroblasts. Conclusions: TMAO promotes the transformation of atrial fibroblasts into myofibroblasts by activating Wnt3a/13-catenin signaling pathway.