© 1996 American Heart Association, Inc.
Articles |
High and Low Molecular Weight Fibroblast Growth Factor-2 Increase Proliferation of Neonatal Rat Cardiac Myocytes but Have Differential Effects on Binucleation and Nuclear Morphology
Evidence for Both Paracrine and Intracrine Actions of Fibroblast GrowthFactor-2
From the Department of Physiology (K.B.S.P., P.A.C.), University of Manitoba, Winnipeg, Canada, and the Departments of Anatomy and Physiology (E.K.), Division of Cardiovascular Sciences, St Boniface Hospital Research Centre, Winnipeg, Canada.
Abstract Basic fibroblast growth factor (FGF-2) plays a vital
role in the growth and differentiation of cardiac myocytes. It exists
in high and low molecular weight forms because of the use of
alternative initiation codons in the same mRNA. Higher levels of high
molecular weight forms (molecular mass of 22 and 21.5 kD) are
present in the rat heart during the neonatal stage, whereas the low
molecular weight form (molecular mass of 18 kD) is predominant in the
adult heart, suggesting different roles in development. Rat FGF-2 cDNAs
that can preferentially express high or low molecular weight forms were
introduced into neonatal rat ventricular myocyte cultures.
Significant and comparable increases in overall cardiac myocyte DNA
synthesis and proliferation were seen with 22/21.5- and 18-kD FGF-2
expression. A significantly higher mitotic index was seen in the
vicinity of cardiac myocytes overexpressing high or low molecular
weight forms of FGF-2 compared with nonoverexpressing cells. This
increase was inhibited in the presence of neutralizing antibodies to
FGF-2, pointing to a proximity-dependent paracrine effect of
22/21.5- and 18-kD FGF-2 on mitosis. By contrast, overexpression of
high but not low molecular weight FGF-2 was associated with a
significant increase in binucleation (
36% of cardiac myocytes
overexpressing 22/21.5-kD FGF-2 were binucleated compared with 9% of
cardiac myocytes overexpressing 18-kD FGF-2), which was not affected by
neutralizing antibodies to FGF-2. These results suggest that 22/21.5-kD
FGF-2 and 18-kD FGF-2 have similar paracrine effects on proliferation
but that 22-21.5-kD FGF-2 exerts a distinct intracrine effect on
binucleation.
Key Words: fibroblast growth factor • cardiac myocytes • binucleation • proliferation
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