© 2000 American Heart Association, Inc.
Cellular Biology |
Autonomous and Growth Factor–Induced Hypertrophy in Cultured Neonatal Mouse Cardiac Myocytes
Comparison With Rat
From the VA Medical Center and the Cardiovascular Research Institute and Department of Medicine, University of California, San Francisco, Calif. Present address of D.G.R. is Department of Medicine, University of Louisville, Louisville, Ky.
Correspondence to Paul C. Simpson, VAMC 111C-8, 4150 Clement St, San Francisco, CA 94121. E-mail pcs{at}itsa.ucsf.edu \ © 2000 American Heart Association, Inc.
Abstract—Cultured
neonatal rat cardiac myocytes have been used extensively to study
cellular and molecular mechanisms of cardiac hypertrophy. However,
there are only a few studies in cultured mouse myocytes despite the
increasing use of genetically engineered mouse models of cardiac
hypertrophy. Therefore, we characterized hypertrophic responses in
low-density, serum-free cultures of neonatal mouse cardiac myocytes and
compared them with rat myocytes. In mouse myocyte cultures,
triiodothyronine (T3), norepinephrine (NE) through a ß-adrenergic
receptor, and leukemia inhibitory factor induced hypertrophy by a 20%
to 30% increase in
[3H]phenylalanine-labeled protein content.
T3 and NE also increased 
-myosin heavy chain (MyHC) mRNA and
reduced ß-MyHC. In contrast, hypertrophic stimuli in rat myocytes,
including 1-adrenergic agonists,
endothelin-1, prostaglandin F2, interleukin
1ß, and phorbol 12-myristate 13-acetate (PMA), had no effect on mouse
myocyte protein content. In further contrast with the rat, none of
these agents increased atrial natriuretic factor or ß-MyHC mRNAs.
Acute PMA signaling was intact by extracellular signal–regulated
kinase (ERK1/2) and immediate-early gene (fos/jun) activation.
Remarkably, mouse but not rat myocytes had hypertrophy in the absence
of added growth factors, with increases in cell area, protein content,
and the mRNAs for atrial natriuretic factor and ß-MyHC. We conclude
that mouse myocytes have a unique autonomous hypertrophy. On this
background, T3, NE, and leukemia inhibitory factor activate hypertrophy
with different mRNA phenotypes, but certain Gq- and protein kinase
C–coupled agonists do
not.
Key Words: mouse • culture • cardiac muscle • hypertrophy
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