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Metformin attenuates cardiac fibrosis by inhibiting the TGF beta(1)-Smad3 signalling pathway
Xiao, Han1,4; Ma, Xiaowei1,4; Feng, Wei1,4; Fu, Yongnan1,4; Lu, Zhizhen1,4; Xu, Ming1,4; Shen, Qiang3,4; Zhu, Yi2,4; Zhang, Youyi1,4
关键词Metformin Cardiac fibrosis TGF-beta(1) Cardiac fibroblast Collagen
刊名CARDIOVASCULAR RESEARCH
2010-08-01
DOI10.1093/cvr/cvq066
87期:3页:504-513
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems
研究领域[WOS]Cardiovascular System & Cardiology
关键词[WOS]ACTIVATED PROTEIN-KINASE ; ANTIDIABETIC DRUG METFORMIN ; AMPK-INDEPENDENT MECHANISMS ; GROWTH-FACTOR-BETA ; HEART-FAILURE ; GLUCOSE CONTROL ; IN-VIVO ; CARDIOPROTECTION ; PROLIFERATION ; HYPERTROPHY
英文摘要

The mechanism of the cardioprotective action of metformin is incompletely understood. We determined the role of metformin in cardiac fibrosis and investigated the mechanism.

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) induced 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)-beta(1) production in mouse hearts and the TGF-beta(1)-induced collagen synthesis in cultured adult mouse cardiac fibroblasts (CFs). Metformin suppressed the phosphorylation of Smad3 in response to TGF-beta(1) in CFs. Metformin also inhibited the nuclear translocation and transcriptional activity of Smad3 in CFs.

Metformin inhibited cardiac fibrosis induced by pressure overload in vivo and inhibited collagen synthesis in CFs probably via inhibition of the TGF-beta(1)-Smad3 signalling pathway. These findings provide a new mechanism for the cardioprotective effects of metformin.

语种英语
WOS记录号WOS:000280014900015
项目编号307001 ; 2006CB503806 ; 30672466 ; 30821001
资助机构Chinese Ministry of Education ; Foundation of National Key Basic Research and Development ; National Natural Science Foundation of China
引用统计
被引频次:91[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59182
专题北京大学第三临床医学院_心血管内科
北京大学基础医学院
作者单位1.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China
2.Peking Univ, Inst Vasc Med, Hosp 3, Beijing 100191, Peoples R China
3.Peking Univ, Dept Physiol & Pathophysiol, Hlth Sci Ctr, Beijing 100191, Peoples R China
4.Peking Univ, Inst Cardiovasc Sci, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Xiao, Han,Ma, Xiaowei,Feng, Wei,et al. Metformin attenuates cardiac fibrosis by inhibiting the TGF beta(1)-Smad3 signalling pathway[J]. CARDIOVASCULAR RESEARCH,2010,87(3):504-513.
APA Xiao, Han.,Ma, Xiaowei.,Feng, Wei.,Fu, Yongnan.,Lu, Zhizhen.,...&Zhang, Youyi.(2010).Metformin attenuates cardiac fibrosis by inhibiting the TGF beta(1)-Smad3 signalling pathway.CARDIOVASCULAR RESEARCH,87(3),504-513.
MLA Xiao, Han,et al."Metformin attenuates cardiac fibrosis by inhibiting the TGF beta(1)-Smad3 signalling pathway".CARDIOVASCULAR RESEARCH 87.3(2010):504-513.
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