© 1995 American Heart Association, Inc.
Articles |
Some Growth Factors Stimulate Cultured Adult Rabbit Ventricular Myocyte Hypertrophy in the Absence of Mechanical Loading
From the Departments of Medicine/Cardiology (R.S.D., M.G.C., M.B.-B., M.L.D.) and Cell and Molecular Biology (R.S.D.), Northwestern University Medical School, Chicago, Ill.
Correspondence to Robert S. Decker, PhD, Department of Medicine/Cardiology S 207, Northwestern University Medical School, 303 E Chicago Ave, Chicago IL 60611.
Abstract Cultured adult rabbit cardiac myocytes treated with
recombinant growth factors display enhanced rates of protein
accumulation (ie, growth) in response to insulin and insulin-like
growth factors (IGFs), but epidermal growth factor, acidic or basic
fibroblast growth factor, and platelet-derived growth factor failed
to increase contractile protein synthesis or growth of the heart cells.
Insulin and IGF-1 increased growth rates by stimulating anabolic while
simultaneously inhibiting catabolic pathways, whereas IGF-2
elevated growth modestly by apparently inhibiting lysosomal
proteolysis. Neutralizing antibodies directed against either IGF-1 or
IGF-2 or IGF binding protein 3 blocked protein accumulation. A
monoclonal antibody directed against the IGF-1 receptor also inhibited
changes in protein turnover provoked by recombinant human IGF-1 but not
IGF-2. Of the other growth factors tested, only transforming growth
factor-ß1 increased the fractional rate of myosin heavy chain (MHC)
synthesis, with ß-MHC synthesis being elevated and 
-MHC synthesis
being suppressed. However, the other growth factors were able to
modestly stimulate the rate of DNA synthesis in this preparation.
Bromodeoxyuridine labeling revealed that these growth factors increased
DNA synthesis in myocytes and nonmyocytes alike, but the heart
cells displayed neither karyokinesis or cytokinesis. In
contrast, cocultures of cardiac myocytes and nonmyocytes and
nonmyocyte-conditioned culture medium failed to enhance the
rate of cardiac MHC synthesis or its accumulation, implying that
quiescent heart cells do not respond to "conditioning" by cardiac
nonmyocytes. These findings demonstrated that insulin and the
IGFs promote passively loaded cultured adult rabbit heart cells to
hypertrophy but suggest that other growth factors tested
may be limited in this regard.
Key Words: cardiac hypertrophy • growth factors • protein turnover • contractile proteins • DNA synthesis
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