标题:ALDH2 Activation Inhibited Cardiac Fibroblast-to-Myofibroblast Transformation Via the TGF-β1/Smad Signaling Pathway
作者:Yuan Q.; Cao S.; Dong Q.; Wang Z.; Xu Y.; Han Q.; Ma J.; Wei S.;等 更多
作者机构:[Yuan, Q] Department of Emergency Medicine and Chest Pain Center, Qilu Hospital of Shandong University, Jinan, China, Clinical Research Center for Eme 更多
来源:Journal of cardiovascular pharmacology
出版年:2019
卷:73
期:4
页码:248-256
DOI:10.1097/FJC.0000000000000655
摘要: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.
收录类别:SCOPUS
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85064240007&doi=10.1097%2fFJC.0000000000000655&partnerID=40&md5=abe2a483de2b6dfb82caf52420ba9239
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