Overexpression of bone morphogenetic protein 10 in myocardium disrupts cardiac postnatal hypertrophic growth

Hanying Chen, Weidong Yong, Shuxun Ren, Weihua Shen, Yongzheng He, Karen A. Cox, Wuqiang Zhu, Wei Li, Mark Soonpaa, R. Payne, Diego Franco, Loren Field, Vicki Rosen, Yibin Wang, Weinian Shou

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Postnatal cardiac hypertrophies have traditionally been classified into physiological or pathological hypertrophies. Both of them are induced by hemodynamic load. Cardiac postnatal hypertrophic growth is regarded as a part of the cardiac maturation process that is independent of the cardiac working load. However, the functional significance of this biological event has not been determined, mainly because of the difficulty in creating an experimental condition for testing the growth potential of functioning heart in the absence of hemodynamic load. Recently, we generated a novel transgenic mouse model (αMHC-BMP10) in which the cardiac-specific growth factor bone morphogenetic protein 10 (BMP10) is overexpressed in postnatal myocardium. These αMHC-BMP10 mice appear to have normal cardiogenesis throughout embryogenesis, but develop to smaller hearts within 6 weeks after birth. αMHC-BMP10 hearts are about half the normal size with 100% penetrance. Detailed morphometric analysis of cardiomyocytes clearly indicated that the compromised cardiac growth in αMHC-BMP10 mice was solely because of defect in cardiomyocyte postnatal hypertrophic growth. Physiological analysis further demonstrated that the responses of these hearts to both physiological (e.g. exercise-induced hypertrophy) and pathological hypertrophic stimuli remain normal. In addition, the αMHC-BMP10 mice develop subaortic narrowing and concentric myocardial thickening without obstruction by four weeks of age. Systematic analysis of potential intracellular pathways further suggested a novel genetic pathway regulating this previously undefined cardiac postnatal hypertrophic growth event. This is the first demonstration that cardiac postnatal hypertrophic growth can be specifically modified genetically and dissected out from physiological and pathological hypertrophies.

Original languageEnglish
Pages (from-to)27481-27491
Number of pages11
JournalJournal of Biological Chemistry
Volume281
Issue number37
DOIs
StatePublished - Sep 15 2006

Fingerprint

Bone Morphogenetic Proteins
Myocardium
Growth
Hypertrophy
Hemodynamics
Cardiac Myocytes
Penetrance
Cardiomegaly
Transgenic Mice
Embryonic Development
Intercellular Signaling Peptides and Proteins
Demonstrations
Parturition
Defects
Testing
Mouse Bmp10 protein

ASJC Scopus subject areas

  • Biochemistry

Cite this

Overexpression of bone morphogenetic protein 10 in myocardium disrupts cardiac postnatal hypertrophic growth. / Chen, Hanying; Yong, Weidong; Ren, Shuxun; Shen, Weihua; He, Yongzheng; Cox, Karen A.; Zhu, Wuqiang; Li, Wei; Soonpaa, Mark; Payne, R.; Franco, Diego; Field, Loren; Rosen, Vicki; Wang, Yibin; Shou, Weinian.

In: Journal of Biological Chemistry, Vol. 281, No. 37, 15.09.2006, p. 27481-27491.

Research output: Contribution to journalArticle

Chen, Hanying ; Yong, Weidong ; Ren, Shuxun ; Shen, Weihua ; He, Yongzheng ; Cox, Karen A. ; Zhu, Wuqiang ; Li, Wei ; Soonpaa, Mark ; Payne, R. ; Franco, Diego ; Field, Loren ; Rosen, Vicki ; Wang, Yibin ; Shou, Weinian. / Overexpression of bone morphogenetic protein 10 in myocardium disrupts cardiac postnatal hypertrophic growth. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 37. pp. 27481-27491.
@article{41a99c4ab3ab4fa1b5061ccc0253b330,
title = "Overexpression of bone morphogenetic protein 10 in myocardium disrupts cardiac postnatal hypertrophic growth",
abstract = "Postnatal cardiac hypertrophies have traditionally been classified into physiological or pathological hypertrophies. Both of them are induced by hemodynamic load. Cardiac postnatal hypertrophic growth is regarded as a part of the cardiac maturation process that is independent of the cardiac working load. However, the functional significance of this biological event has not been determined, mainly because of the difficulty in creating an experimental condition for testing the growth potential of functioning heart in the absence of hemodynamic load. Recently, we generated a novel transgenic mouse model (αMHC-BMP10) in which the cardiac-specific growth factor bone morphogenetic protein 10 (BMP10) is overexpressed in postnatal myocardium. These αMHC-BMP10 mice appear to have normal cardiogenesis throughout embryogenesis, but develop to smaller hearts within 6 weeks after birth. αMHC-BMP10 hearts are about half the normal size with 100{\%} penetrance. Detailed morphometric analysis of cardiomyocytes clearly indicated that the compromised cardiac growth in αMHC-BMP10 mice was solely because of defect in cardiomyocyte postnatal hypertrophic growth. Physiological analysis further demonstrated that the responses of these hearts to both physiological (e.g. exercise-induced hypertrophy) and pathological hypertrophic stimuli remain normal. In addition, the αMHC-BMP10 mice develop subaortic narrowing and concentric myocardial thickening without obstruction by four weeks of age. Systematic analysis of potential intracellular pathways further suggested a novel genetic pathway regulating this previously undefined cardiac postnatal hypertrophic growth event. This is the first demonstration that cardiac postnatal hypertrophic growth can be specifically modified genetically and dissected out from physiological and pathological hypertrophies.",
author = "Hanying Chen and Weidong Yong and Shuxun Ren and Weihua Shen and Yongzheng He and Cox, {Karen A.} and Wuqiang Zhu and Wei Li and Mark Soonpaa and R. Payne and Diego Franco and Loren Field and Vicki Rosen and Yibin Wang and Weinian Shou",
year = "2006",
month = "9",
day = "15",
doi = "10.1074/jbc.M604818200",
language = "English",
volume = "281",
pages = "27481--27491",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "37",

}

TY - JOUR

T1 - Overexpression of bone morphogenetic protein 10 in myocardium disrupts cardiac postnatal hypertrophic growth

AU - Chen, Hanying

AU - Yong, Weidong

AU - Ren, Shuxun

AU - Shen, Weihua

AU - He, Yongzheng

AU - Cox, Karen A.

AU - Zhu, Wuqiang

AU - Li, Wei

AU - Soonpaa, Mark

AU - Payne, R.

AU - Franco, Diego

AU - Field, Loren

AU - Rosen, Vicki

AU - Wang, Yibin

AU - Shou, Weinian

PY - 2006/9/15

Y1 - 2006/9/15

N2 - Postnatal cardiac hypertrophies have traditionally been classified into physiological or pathological hypertrophies. Both of them are induced by hemodynamic load. Cardiac postnatal hypertrophic growth is regarded as a part of the cardiac maturation process that is independent of the cardiac working load. However, the functional significance of this biological event has not been determined, mainly because of the difficulty in creating an experimental condition for testing the growth potential of functioning heart in the absence of hemodynamic load. Recently, we generated a novel transgenic mouse model (αMHC-BMP10) in which the cardiac-specific growth factor bone morphogenetic protein 10 (BMP10) is overexpressed in postnatal myocardium. These αMHC-BMP10 mice appear to have normal cardiogenesis throughout embryogenesis, but develop to smaller hearts within 6 weeks after birth. αMHC-BMP10 hearts are about half the normal size with 100% penetrance. Detailed morphometric analysis of cardiomyocytes clearly indicated that the compromised cardiac growth in αMHC-BMP10 mice was solely because of defect in cardiomyocyte postnatal hypertrophic growth. Physiological analysis further demonstrated that the responses of these hearts to both physiological (e.g. exercise-induced hypertrophy) and pathological hypertrophic stimuli remain normal. In addition, the αMHC-BMP10 mice develop subaortic narrowing and concentric myocardial thickening without obstruction by four weeks of age. Systematic analysis of potential intracellular pathways further suggested a novel genetic pathway regulating this previously undefined cardiac postnatal hypertrophic growth event. This is the first demonstration that cardiac postnatal hypertrophic growth can be specifically modified genetically and dissected out from physiological and pathological hypertrophies.

AB - Postnatal cardiac hypertrophies have traditionally been classified into physiological or pathological hypertrophies. Both of them are induced by hemodynamic load. Cardiac postnatal hypertrophic growth is regarded as a part of the cardiac maturation process that is independent of the cardiac working load. However, the functional significance of this biological event has not been determined, mainly because of the difficulty in creating an experimental condition for testing the growth potential of functioning heart in the absence of hemodynamic load. Recently, we generated a novel transgenic mouse model (αMHC-BMP10) in which the cardiac-specific growth factor bone morphogenetic protein 10 (BMP10) is overexpressed in postnatal myocardium. These αMHC-BMP10 mice appear to have normal cardiogenesis throughout embryogenesis, but develop to smaller hearts within 6 weeks after birth. αMHC-BMP10 hearts are about half the normal size with 100% penetrance. Detailed morphometric analysis of cardiomyocytes clearly indicated that the compromised cardiac growth in αMHC-BMP10 mice was solely because of defect in cardiomyocyte postnatal hypertrophic growth. Physiological analysis further demonstrated that the responses of these hearts to both physiological (e.g. exercise-induced hypertrophy) and pathological hypertrophic stimuli remain normal. In addition, the αMHC-BMP10 mice develop subaortic narrowing and concentric myocardial thickening without obstruction by four weeks of age. Systematic analysis of potential intracellular pathways further suggested a novel genetic pathway regulating this previously undefined cardiac postnatal hypertrophic growth event. This is the first demonstration that cardiac postnatal hypertrophic growth can be specifically modified genetically and dissected out from physiological and pathological hypertrophies.

UR - http://www.scopus.com/inward/record.url?scp=33748749375&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748749375&partnerID=8YFLogxK

U2 - 10.1074/jbc.M604818200

DO - 10.1074/jbc.M604818200

M3 - Article

C2 - 16798733

AN - SCOPUS:33748749375

VL - 281

SP - 27481

EP - 27491

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 37

ER -