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学科主题临床医学
Growth Differentiation Factor (GDF)-15 Blocks Norepinephrineinduced Myocardial Hypertrophy via a Novel Pathway Involving Inhibition of Epidermal Growth Factor Receptor Transactivation*
Xu, Xin-ye; Nie, Ying; Wang, Fang-fang; Bai, Yan; Lv, Zhi-zhen; Zhang, You-yi; Li, Zi-jian1; Gao, Wei
关键词Cardiac Hypertrophy Cell Signaling Epidermal Growth Factor Receptor (Egfr) Growth Factors Hypertension Growth Differentiation Factor 15 Norepinephrine Transactivation
刊名JOURNAL OF BIOLOGICAL CHEMISTRY
2014-04-04
DOI10.1074/jbc.M113.516278
289期:14页:10084-10094
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology
研究领域[WOS]Biochemistry & Molecular Biology
关键词[WOS]CHRONIC HEART-FAILURE ; SYMPATHETIC-NERVOUS-SYSTEM ; FACTOR-BETA SUPERFAMILY ; ACUTE CORONARY SYNDROME ; MOLECULAR-MECHANISMS ; ADULT CARDIOMYOCYTES ; EUROPEAN-SOCIETY ; DISEASE SEVERITY ; TASK-FORCE ; HYPERTENSION
英文摘要

Background: The effect of GDF-15 on the regulation of cardiac remodeling is poorly understood. Results: GDF-15 inhibits norepinephrine induced EGF receptor transactivation and associated hypertrophy and positively associates with myocardial hypertrophy of hypertension patients. Conclusion: GDF-15 blocks norepinephrine-induced myocardial hypertrophy via a novel pathway involving inhibition of EGF receptor transactivation. Significance: We indicate a negative feedback mechanism of GDF-15 in regulating catecholamine-induced cardiac remodeling.

Accumulating evidence suggests that growth differentiation factor 15 (GDF-15) is associated with the severity and prognosis of various cardiovascular diseases. However, the effect of GDF-15 on the regulation of cardiac remodeling is still poorly understood. In this present study, we demonstrate that GDF-15 blocks norepinephrine (NE)-induced myocardial hypertrophy through a novel pathway involving inhibition of EGFR transactivation. Both in vivo and in vitro assay indicate that NE was able to stimulate the synthesis of GDF-15. The up-regulation of GDF-15 feedback inhibits NE-induced myocardial hypertrophy, including quantitation of [H-3]leucine incorporation, protein/DNA ratio, cell surface area, and ANP mRNA level. Further research shows that GDF-15 could inhibit the phosphorylation of EGF receptor and downstream kinases (AKT and ERK1/2) induced by NE. Clinical research also shows that serum GDF-15 levels in hypertensive patients were significant higher than in healthy volunteers and were positively correlated with the thickness of the posterior wall of the left ventricle, interventricular septum, and left ventricular mass, as well as the serum level of norepinephrine. In conclusion, NE induces myocardial hypertrophy and up-regulates GDF-15, and this up-regulation of GDF-15 negatively regulates NE-induced myocardial hypertrophy by inhibiting EGF receptor transactivation following NE stimulation.

语种英语
WOS记录号WOS:000333807000055
项目编号PUCRP-004 ; 30910103902 ; 81270157 ; 81070078 ; 81121061 ; 2011CB503903 ; 7102158
资助机构Key Construction Program of the National 985 Project ; National Natural Science Foundation of China ; 973 Program of the Major State Basic Research Development Program of China ; Beijing Municipal Natural Science Foundation
引用统计
被引频次:14[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/400002259/57731
专题北京大学第三临床医学院_心血管内科
作者单位1.Peking Univ, Dept Cardiol, Hosp 3, Beijing 100191, Peoples R China
2.Minist Educ, Key Lab Cardiovasc Mol Biol & Regulatory Peptides, Minist Hlth, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China
3.Beijing Key Lab Cardiovasic Receptors Res, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Xu, Xin-ye,Nie, Ying,Wang, Fang-fang,et al. Growth Differentiation Factor (GDF)-15 Blocks Norepinephrineinduced Myocardial Hypertrophy via a Novel Pathway Involving Inhibition of Epidermal Growth Factor Receptor Transactivation*[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2014,289(14):10084-10094.
APA Xu, Xin-ye.,Nie, Ying.,Wang, Fang-fang.,Bai, Yan.,Lv, Zhi-zhen.,...&Gao, Wei.(2014).Growth Differentiation Factor (GDF)-15 Blocks Norepinephrineinduced Myocardial Hypertrophy via a Novel Pathway Involving Inhibition of Epidermal Growth Factor Receptor Transactivation*.JOURNAL OF BIOLOGICAL CHEMISTRY,289(14),10084-10094.
MLA Xu, Xin-ye,et al."Growth Differentiation Factor (GDF)-15 Blocks Norepinephrineinduced Myocardial Hypertrophy via a Novel Pathway Involving Inhibition of Epidermal Growth Factor Receptor Transactivation*".JOURNAL OF BIOLOGICAL CHEMISTRY 289.14(2014):10084-10094.
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