H11 Kinase Is a Novel Mediator of Myocardial Hypertrophy In Vivo
作者:
Christophe Depre,
Makoto Hase,
Vinciane Gaussin,
Anna Zajac,
Li Wang,
Luc Hittinger,
Bijan Ghaleh,
Xianzhong Yu,
Raymond Kudej,
Thomas Wagner,
Junichi Sadoshima,
Stephen Vatner,
期刊:
Circulation Research: Journal of the American Heart Association
(OVID Available online 2002)
卷期:
Volume 91,
issue 11
页码: 1007-1014
ISSN:0009-7330
年代: 2002
出版商: OVID
关键词: cardiac growth;H11 kinase;hypertrophy;gene expression;ischemia
数据来源: OVID
摘要:
Abstract—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 &agr;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 p70S6kinase, whereas the MAP kinase pathway was unaffected. Thus, H11 kinase represents a novel mediator of cardiac cell growth and hypertrophy.
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