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Cardiac-specific BMP4 transgenic mice does not develop a pathological heart hypertrophy phenotype because of immaturity of the overexpressed BMP4
Yonghui Zhang 1,Ning Ma 2,Shan-Liang Li 1,Rong Huo 1,Bo Sun 1,Yue Sheng 1,Feng Cheng 1,Xue-Ting Du 1,De-Li Dong 1 *
1.Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University
2.Department of Biochemistry and Molecular Biology, Harbin Medical University
*Correspondence author
#Submitted by
Subject:
Funding: the National Natural Science Foundation of China （No.81373406) and the Research Fund for the Doctoral Program of Higher Education of China）
Opened online:15 November 2014
Accepted by: none
Citation: Yonghui Zhang,Ning Ma,Shan-Liang Li.Cardiac-specific BMP4 transgenic mice does not develop a pathological heart hypertrophy phenotype because of immaturity of the overexpressed BMP4[OL]. [15 November 2014] http://en.paper.edu.cn/en_releasepaper/content/4614634
 
 
Background/Aims: Our previous work showed that bone morphogenetic protein 4 (BMP-4) induced cardiomyocyte hypertrophy. In the present work, we established the transgenic mice (TG) with cardiac-specific overexpression of BMP4 and investigated whether these transgenic mice could develop a pathological heart hypertrophy phenotype or show exacerbated pathological heart hypertrophy under pressure-overload stimulus. Methods: Transgenic mice with cardiac-specific overexpression of BMP4 were identified by PCR and western blot analysis. The pressure-overload heart hypertrophy was induced by transverse aortic constriction (TAC) operation. Cardiac function was assessed by echocardiography using a Visual- Sonics Vevo 2100 Imaging System. Results: TG mice expressed significantly higher protein level of BMP4 precursor form but not the mature form. TG mice did not develop a pathological heart hypertrophy phenotype at 16 weeks after birth. Pressure-overload for 4 weeks induced significant heart hypertrophy in both TG and wild type (WT) mice, but there was no difference in the hypertrophic parameters between TG and WT mice treated with pressure-overload. Pressure-overload induced significant increase of BMP4 expression in protein level in both TG and WT mice, but no difference of BMP4 mature form was observed between TG and WT mice treated with pressure-overload. Conclusion: The increased precursor form in cardiac BMP4 TG mice did not become matured even under the pressure-overload stimulus, so these transgenic mice could not develop a pathological heart hypertrophy phenotype or show exacerbated pathological heart hypertrophy under pathological stimuli.
Keywords:Bone morphogenetic protein 4; transgenic mice;heart hypertrophy; pressure overload
 
 
 

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