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学科主题: 临床医学
题名:
Metformin attenuates cardiac fibrosis by inhibiting the TGF beta(1)-Smad3 signalling pathway
作者: 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
发表日期: 2010-08-01
DOI: 10.1093/cvr/cvq066
卷: 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
所属项目编号: 307001 ; 2006CB503806 ; 30672466 ; 30821001
项目资助者: Chinese Ministry of Education ; Foundation of National Key Basic Research and Development ; National Natural Science Foundation of China
WOS记录号: WOS:000280014900015
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59182
Appears in Collections:北京大学第三临床医学院_心血管内科_期刊论文

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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

Recommended Citation:
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.
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