Yang Wentao, Zhao Qing, Yao Minghui, Li Xiangdong, Shan Zhaoliang, Wang Yutang
College of Medicine, Nankai University, Tianjin, China.
Department of Cardiology, The Sixth Medical Center, Chinese PLA General Hospital, Beijing, China.
J Thorac Dis. 2022 May;14(5):1526-1536. doi: 10.21037/jtd-22-475.
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/β-catenin pathway also plays a key role in the promotion of cardiac fibroblasts into myofibroblasts.
The expression of Alpha-smooth muscle actin (α-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 β-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 β-catenin pathway and the phenotypic transformation of atrial fibroblasts.
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 β-catenin pathway. Exogenous Wnt3a and TMAO synergistically promoted the activation and phenotypic transformation of the β-catenin pathway in atrial fibroblasts.
TMAO promotes the transformation of atrial fibroblasts into myofibroblasts by activating Wnt3a/β-catenin signaling pathway.
心房纤维化是心房颤动发生和维持的重要病理生理机制。氧化三甲胺（TMAO）是研究最广泛的参与促进心脏纤维化的微生物代谢产物之一。TMAO促进心脏成纤维细胞的表型转化、增殖和迁移，并增加胶原蛋白分泌。Wnt/β-连环蛋白通路在促进心脏成纤维细胞向肌成纤维细胞转化中也起关键作用。
通过检测α-平滑肌肌动蛋白（α-SMA）的表达来鉴定肌成纤维细胞的形成。分别采用细胞计数试剂盒8和Transwell实验检测TMAO对心房成纤维细胞增殖和迁移的影响。采用蛋白质免疫印迹法和免疫荧光法检测TMAO对β-连环蛋白通路的激活作用以及心房成纤维细胞的表型转化和胶原蛋白分泌情况。进行蛋白质免疫印迹法和免疫荧光实验以检测外源性Wnt3a和TMAO对β-连环蛋白通路激活及心房成纤维细胞表型转化的影响。
TMAO促进心房成纤维细胞的增殖和迁移。TMAO还通过激活β-连环蛋白通路促进心房成纤维细胞的表型转化、迁移和胶原蛋白分泌。外源性Wnt3a和TMAO协同促进心房成纤维细胞中β-连环蛋白通路的激活和表型转化。
TMAO通过激活Wnt3a/β-连环蛋白信号通路促进心房成纤维细胞向肌成纤维细胞转化。
