Metformin attenuates cardiac fibrosis by inhibiting the TGFβ1–Smad3 signalling pathway

Han Xiao, Xiaowei Ma, Wei Feng, Yongnan Fu, Zhizhen Lu, Ming Xu, Qiang Shen, Yi Zhu, Youyi Zhang
2010 Cardiovascular Research  
Aims The mechanism of the cardioprotective action of metformin is incompletely understood. We determined the role of metformin in cardiac fibrosis and investigated the mechanism. Methods and results Ten-week-old male mice (C57BL/6) were subjected to left ventricular pressure overload by transverse aortic constriction. Mice received metformin (200 mg/kg/day) or normal saline for 6 weeks. Metformin inhibited cardiac fibrosis (fibrosis area/total heart area: 0.6 + 0.3 vs. 3.6 + 0.9%, P , 0.01)
more » ... ced by pressure overload and improved cardiac diastolic function (left ventricular end-diastolic pressure: 5.2 + 0.9 vs. 11.0 + 1.6 mmHg, P , 0.05). Metformin inhibited the pressure overload-induced transforming growth factor (TGF)-b 1 production in mouse hearts and the TGF-b 1induced collagen synthesis in cultured adult mouse cardiac fibroblasts (CFs). Metformin suppressed the phosphorylation of Smad3 in response to TGF-b 1 in CFs. Metformin also inhibited the nuclear translocation and transcriptional activity of Smad3 in CFs. Conclusion Metformin inhibited cardiac fibrosis induced by pressure overload in vivo and inhibited collagen synthesis in CFs probably via inhibition of the TGF-b 1 -Smad3 signalling pathway. These findings provide a new mechanism for the cardioprotective effects of metformin. ---
doi:10.1093/cvr/cvq066 pmid:20200042 fatcat:nsyg7flepzbqde3ojehil33vpy