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(Circulation Research. 2001;89:1122.)
© 2001 American Heart Association, Inc.

Molecular Medicine

Inducible Activation of c-Myc in Adult Myocardium In Vivo Provokes Cardiac Myocyte Hypertrophy and Reactivation of DNA Synthesis

Guishan Xiao^*, Songyan Mao^*, Georg Baumgarten, Jennifer Serrano, Maria C. Jordan, Kenneth P. Roos, Michael C. Fishbein, W. Robb MacLellan

From the Cardiovascular Research Laboratories, Departments of Medicine (G.X., S.M., J.S., W.R.M.), Physiology (M.C.J., K.P.R., W.R.M.), and Pathology (M.C.F.), University of California at Los Angeles School of Medicine, and Department of Anesthesiology and Intensive Care Medicine (G.B.), Friederich-Wilhelms University of Bonn, Germany.

Correspondence to W. Robb MacLellan, Cardiovascular Research Laboratories, UCLA School of Medicine, 675 C.E. Young Dr, MRL 3-645, Los Angeles, CA 90095-1760. E-mail rmaclellan{at}mednet.ucla.edu

c-Myc, a protooncogene, mediates both proliferative and cellular growth in many cell types. Although not expressed in the adult heart under normal physiological conditions, Myc expression is rapidly upregulated in response to hypertrophic stimuli. Although Myc is capable of sustaining hyperplastic growth in fetal myocytes, the effects of its re-expression in adult postmitotic myocardium and its role in mediating cardiac hypertrophy are unknown. To determine the effects of de novo Myc activity in adult postmitotic myocardium in vivo, we created a novel transgenic model in which Myc is expressed and inducibly activated specifically in cardiac myocytes. Activation of Myc in adult myocardium was sufficient to reproduce the characteristic changes in myocyte size, protein synthesis, and cardiac-specific gene expression seen in cardiac hypertrophy. Despite the increased cardiac mass, left ventricular function remained normal. Activation of Myc also provoked cell cycle reentry in postmitotic myocytes, which led to increased nuclei per myocyte and DNA content per nuclei.

Key Words: cardiac muscle • Myc • hypertrophy • cell cycle • cardiac growth

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