Overexpression of bone morphogenetic protein 10 in myocardium disrupts cardiac postnatal hypertrophic growth.
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 (alphaMHC-BMP10) in which the cardiac-specific growth factor bone morphogenetic protein 10 (BMP10) is overexpressed in postnatal myocardium. These alphaMHC-BMP10 mice appear to have normal cardiogenesis throughout embryogenesis, but develop to smaller hearts within 6 weeks after birth. alphaMHC-BMP10 hearts are about half the normal size with 100% penetrance. Detailed morphometric analysis of cardiomyocytes clearly indicated that the compromised cardiac growth in alphaMHC-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 alphaMHC-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.
Chen
Hanying
H
Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Division of Pediatric Cardiology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Yong
Weidong
W
Ren
Shuxun
S
Shen
Weihua
W
He
Yongzheng
Y
Cox
Karen A
KA
Zhu
Wuqiang
W
Li
Wei
W
Soonpaa
Mark
M
Payne
R Mark
RM
Franco
Diego
D
Field
Loren J
LJ
Rosen
Vicki
V
Wang
Yibin
Y
Shou
Weinian
W
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000254:growth & development; D006439:Hemodynamics; D006984:Hypertrophy; D007328:Insulin / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism
C119152:Bmp10 protein, mouse; D019485:Bone Morphogenetic Proteins; D007328:Insulin