Published online before print October 31, 2002, doi: 10.1161/01.RES.0000044380.54893.4B
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© 2002 American Heart Association, Inc.
Molecular Medicine |
H11 Kinase Is a Novel Mediator of Myocardial Hypertrophy In Vivo
From the Cardiovascular Research Institute (C.D., M.H., V.G., A.Z., L.W., L.H., B.G., R.K.K., J.S., S.F.V.), Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry New Jersey, New Jersey Medical School, Newark, NJ; and the Oncology Research Institute (X.Y., T.W.), Greenville Hospital System, Greenville, SC.
Correspondence to Christophe Depre, MD, PhD, Cardiovascular Research Institute, Dept of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange St, MSB G-609, Newark, NJ 07103. E-mail deprech{at}umdnj.edu
By subtractive hybridization, we found a significant increase in H11 kinase transcript in large mammalian models of both ischemia/reperfusion (stunning) and chronic pressure overload with hypertrophy. Because this gene has not been characterized in the heart, the goal of the present study was to determine the function of H11 kinase in cardiac tissue, both in vitro and in vivo. In isolated neonatal rat cardiac myocytes, adenoviral-mediated overexpression of H11 kinase resulted in a 37% increase in protein/DNA ratio, reflecting hypertrophy. A cardiac-specific transgene driven by the 
MHC-promoter was generated, which resulted in an average 7-fold increase in H11 kinase protein expression. Transgenic hearts were characterized by a 30% increase of the heart weight/body weight ratio, by the reexpression of a fetal gene program, and by concentric hypertrophy with preserved contractile function at echocardiography. This phenotype was accompanied by a dose-dependent activation of Akt/PKB and p70S6 kinase, whereas the MAP kinase pathway was unaffected. Thus, H11 kinase represents a novel mediator of cardiac cell growth and hypertrophy.
Key Words: cardiac growth • H11 kinase • hypertrophy • gene expression • ischemia
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