IR@PKUHSC  > 北京大学第三临床医学院  > 心血管内科
学科主题临床医学
Targeted disruption of Smad4 in cardiomyocytes results in cardiac hypertrophy and heart failure
Wang, J1; Xu, N1; Feng, XH1; Hou, N1; Zhang, JS1; Cheng, X1; Chen, YG1; Zhang, YY1; Yang, X1
关键词Smad4 Cardiac Hypertrophy Heart Failure Mitogen-activated Protein Kinase Cre-loxp System
刊名CIRCULATION RESEARCH
2005-10-14
DOI10.1161/01.RES.0000185833.42544.06
97期:8页:821-828
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems ; Hematology ; Peripheral Vascular Disease
研究领域[WOS]Cardiovascular System & Cardiology ; Hematology
关键词[WOS]GROWTH-FACTOR-BETA ; ACTIVATED PROTEIN-KINASE ; SIGNALING PATHWAYS ; GENE-EXPRESSION ; ANGIOTENSIN-II ; MOUSE EMBRYO ; TRANSFORMING GROWTH-FACTOR-BETA-1 ; VENTRICULAR MYOCYTES ; ENDOCARDIAL CUSHION ; MYOCARDIAL FIBROSIS
英文摘要

Transforming growth factor-beta s ( TGF-beta s) are pleiotropic cytokines involved in many physiological and pathological processes, including heart development and heart disease. Smad4 is the central intracellular mediator of TGF-beta signaling. To investigate the function of Smad4 in heart development further, we generated a strain of cardiomyocyte-specific Smad4 knockout mice using the Cre-loxP system. Unexpectedly, the deletion of Smad4 in cardiomyocytes resulted in cardiac hypertrophy characterized by an increase in the size of cardiac myocytes, age-associated fibrosis, and reexpression of certain fetal genes. Approximately 70% of the Smad4 mutant mice died spontaneously between 5 and 12 months of age. Echocardiography and an invasive hemodynamic study of the left ventricle revealed markedly decreased cardiac contractility in Smad4 mutant mice compared with littermate controls. Moreover, phosphorylated extracellular signal-regulated kinase ( ERK) 1/2 and mitogen-activated protein kinase-ERK ( MEK) 1 were increased in the Smad4 mutants, suggesting that an upregulation of MEK1-ERK1/2 signaling as a consequence of deletion of Smad4 underlies the impaired cardiac function. These results reveal an important function of Smad4 in cardiac remodeling and suggest that an altered cellular response to TGF-beta could be a mechanism by which cardiac myocytes undergo hypertrophy.

语种英语
WOS记录号WOS:000232554000013
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被引频次:96[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/400002259/53000
专题北京大学第三临床医学院_心血管内科
作者单位1.Inst Biotechnol, Beijing 100071, Peoples R China
2.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing, Peoples R China
3.Peking Univ, Hosp 3, Inst Vasc Med, Beijing 100085, Peoples R China
4.Peking Univ, Hosp 3, Genet Lab Dev & Dis, Beijing 100085, Peoples R China
5.Tsing Hua Univ, Dept Biol Sci & Biotechnol, Beijing 100084, Peoples R China
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GB/T 7714
Wang, J,Xu, N,Feng, XH,et al. Targeted disruption of Smad4 in cardiomyocytes results in cardiac hypertrophy and heart failure[J]. CIRCULATION RESEARCH,2005,97(8):821-828.
APA Wang, J.,Xu, N.,Feng, XH.,Hou, N.,Zhang, JS.,...&Yang, X.(2005).Targeted disruption of Smad4 in cardiomyocytes results in cardiac hypertrophy and heart failure.CIRCULATION RESEARCH,97(8),821-828.
MLA Wang, J,et al."Targeted disruption of Smad4 in cardiomyocytes results in cardiac hypertrophy and heart failure".CIRCULATION RESEARCH 97.8(2005):821-828.
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