TY - JOUR AB - Excessive proliferation and myofibroblasts transformation of cardiac fibroblasts play a critical role in the process of cardiac fibrosis. Atorvastatin (ATV), a 3‑hydroxy‑3‑methyl‑glutaryl‑coenzyme A reductase inhibitor, is commonly used to treat hypercholesterolemia. It has previously been shown that ATV has potential anti‑fibrotic effects. However, the underlying mechanisms of ATV against cardiac fibrosis remain to be fully elucidated, and to the best of our knowledge, there are no reports focusing on the effects of ATV on transforming growth factor‑β1 (TGF‑β1)‑induced human ventricular fibroblasts (hVFs) activation. In the present study, hVFs were stimulated with TGF‑β1 with or without pretreatment with ATV. Subsequently, hVF proliferation, cytotoxicity, myofibroblast differentiation and pro‑fibrotic gene expression were assessed. Canonical and non‑canonical signaling downstream of TGF‑β1, such as Smad3 and mitogen‑activated protein kinase (MAPK) signaling, were investigated by evaluating the phosphorylation levels of Smad3, extracellular signal‑regulated kinase 1/2, p38 MAPK and c‑Jun N‑terminal kinase. The results indicated that ATV significantly prevented TGF‑β1‑induced cell proliferation, myofibroblast differentiation and production of extracellular matrix proteins, such as matrix metalloproteinase‑2, collagen I and collagen III, in hVFs. Furthermore, ATV effectively inhibited TGF‑β1‑induced activation of Smad3 and MAPK signaling in hVFs. In conclusion, the present results demonstrated that ATV prevented TGF‑β1‑induced fibrogenesis in hVFs, at least in part by inhibiting the Smad3 and MAPK signaling pathways. Therefore, these results imply that ATV may be a promising agent to treat myocardial fibrosis. AD - Key Laboratory of Medical Electrophysiology, Ministry of Education, Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China Key Laboratory of Medical Electrophysiology, Ministry of Education, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China Department of Basic Medical Sciences, College of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China AU - Du,Yanfei AU - Xiao,Haiying AU - Wan,Jun AU - Wang,Xinyu AU - Li,Tao AU - Zheng,Shuzhan AU - Feng,Jian AU - Ye,Qiang AU - Li,Jiafu AU - Li,Guang AU - Fan,Zhongcai DA - 2020/08/01 DO - 10.3892/ijmm.2020.4607 EP - 640 IS - 2 JO - Int J Mol Med KW - cardiac fibrosis human ventricular fibroblasts transforming growth factor‑β1 atorvastatin extracellular matrix signaling pathways PY - 2020 SN - 1107-3756 1791-244X SP - 633 ST - Atorvastatin attenuates TGF‑β1‑induced fibrogenesis by inhibiting Smad3 and MAPK signaling in human ventricular fibroblasts T2 - International Journal of Molecular Medicine TI - Atorvastatin attenuates TGF‑β1‑induced fibrogenesis by inhibiting Smad3 and MAPK signaling in human ventricular fibroblasts UR - https://doi.org/10.3892/ijmm.2020.4607 VL - 46 ER -