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学科主题: 临床医学
题名:
Targeted disruption of Smad4 in cardiomyocytes results in cardiac hypertrophy and heart failure
作者: 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
发表日期: 2005-10-14
DOI: 10.1161/01.RES.0000185833.42544.06
卷: 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
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53000
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.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

Recommended Citation:
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.
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