ALDH2 Activation Inhibited Cardiac Fibroblast-to-Myofibroblast Transformation Via the TGF-β1/Smad Signaling Pathway

作者：Qiuhuan Yuan, Shengchuan Cao, Qianqian Dong, Zheng Wang, Youshun Xu, Qi Han, Jingjing Ma, Shujian Wei, Jiaojiao Pang, Feihong Yang, Rui Zhang, Baoshan Liu, Shuai Dai, Li Xue, Jiali Wang, Mengyang Xue, Tonghui Xu, Wen Zheng, Feng Xu, Yuguo Chen, Ping Guo · 发表于：Journal of Cardiovascular Pharmacology · 年份：2019 · DOI：10.1097/fjc.0000000000000655 · 被引用次数：24 · 研究领域：Cardiac Fibrosis and Remodeling、Cardiovascular Function and Risk Factors、Cardiac Structural Anomalies and Repair

Pathological stimulus-triggered differentiation of cardiac fibroblasts plays a major role in the development of myocardial fibrosis. Aldehyde dehydrogenase 2 (ALDH2) was reported to exert a protective role in cardiovascular disease, and whether ALDH2 is involved in cardiac fibroblast differentiation remains unclear. In this study, we used transforming growth factor-β1 (TGF-β1) to induce the differentiation of human cardiac fibroblasts (HCFs) and adopted ALDH2 activator Alda-1 to verify the influence of ALDH2 on HCF differentiation. Results showed that ALDH2 activity was obviously impaired when treating HCFs with TGF-β1. Activation of ALDH2 with Alda-1 inhibited the transformation of HCFs into myofibroblasts, demonstrated by the decreased smooth muscle actin (α-actin) and periostin expression, reduced HCF-derived myofibroblast proliferation, collagen production, and contractility. Moreover, application of Smad2/3 inhibitor alleviated TGF-β1-induced HCF differentiation and improved ALDH2 activity, which was reversed by the application of ALDH2 inhibitor daidzin. Finally, Alda-1-induced HCF alterations alleviated neonatal rat cardiomyocyte hypertrophy, supported by the immunostaining of α-actin. To summarize, activation of ALDH2 enzymatic activity inhibited the differentiation of cardiac fibroblasts via the TGF-β1/Smad signaling pathway, which might be a promising strategy to relieve myocardial fibrosis of various causes.