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Metformin attenuates pressure overload-induced cardiac hypertrophy via AMPK activation
Fu, Yong-nan; Xiao, Han; Ma, Xiao-wei; Jiang, Sheng-yang; Xu, Ming; Zhang, You-yi1
关键词metformin cardiac hypertrophy AMP-activated protein kinase protein synthesis transverse aortic constriction Akt/protein kinase B mammalian target of rapamycin
刊名ACTA PHARMACOLOGICA SINICA
2011-07-01
DOI10.1038/aps.2010.229
32期:7页:879-887
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]Chemistry ; Pharmacology & Pharmacy
关键词[WOS]PROTEIN-KINASE ACTIVITY ; ANGIOTENSIN-II ; HEART-FAILURE ; MYOCARDIAL FIBROSIS ; GLUCOSE CONTROL ; GROWTH ; CARDIOMYOCYTES ; DYSFUNCTION ; METABOLISM ; MOUSE
英文摘要

Aim: To identify the role of metformin in cardiac hypertrophy and investigate the possible mechanism underlying this effect.

Methods: Wild type and AMPK alpha 2 knockout (AMPK alpha 2(-/-)) littermates were subjected to left ventricular pressure overload caused by transverse aortic constriction. After administration of metformin (200 mg.kg(-1).d(-1)) for 6 weeks, the degree of cardiac hypertrophy was evaluated using echocardiography and anatomic and histological methods. The antihypertrophic mechanism of metformin was analyzed using Western blotting.

Results: Metformin significantly attenuated cardiac hypertrophy induced by pressure overload in wild type mice, but the antihypertrophic actions of metformin were ablated in AMPK alpha 2(-/-) mice. Furthermore, metformin suppressed the phosphorylation of Akt/protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in response to pressure overload in wild type mice, but not in AMPK alpha 2(-/-) mice.

Conclusion: Long-term administration of metformin may attenuate cardiac hypertrophy induced by pressure overload in nondiabetic mice, and this attenuation is highly dependent on AMPK activation. These findings may provide a potential therapy for patients at risk of developing pathological cardiac hypertrophy.

语种英语
WOS记录号WOS:000292447600003
项目编号81030001 ; 30821001 ; 30910103902
资助机构National Natural Science Foundation of China ; NSFC
引用统计
被引频次:25[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/400002259/65532
专题北京大学第三临床医学院_心血管内科
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
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Fu, Yong-nan,Xiao, Han,Ma, Xiao-wei,et al. Metformin attenuates pressure overload-induced cardiac hypertrophy via AMPK activation[J]. ACTA PHARMACOLOGICA SINICA,2011,32(7):879-887.
APA Fu, Yong-nan,Xiao, Han,Ma, Xiao-wei,Jiang, Sheng-yang,Xu, Ming,&Zhang, You-yi.(2011).Metformin attenuates pressure overload-induced cardiac hypertrophy via AMPK activation.ACTA PHARMACOLOGICA SINICA,32(7),879-887.
MLA Fu, Yong-nan,et al."Metformin attenuates pressure overload-induced cardiac hypertrophy via AMPK activation".ACTA PHARMACOLOGICA SINICA 32.7(2011):879-887.
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