Norepinephrine and angiotensin ii stimulate the secretion of transforming
growth factor (tgf-[beta]1 and tgf-[beta]2) by neonatal rat cardiac
fibroblasts in vitro: role of tgf-[beta] as a paracrine mediator of cardiac
hypertrophy.
Fisher, Steven A., and Marlene Absher.
Departments of Medicine and Molecular Physiology and Biophysics, University
of Vermont, Burlington, Vermont 05405
APStracts 2:0013C, 1995.
Transforming growth factor-beta (TGF-[beta]) is a ubiquitous growth regulating
protein which is capable of influencing growth and function of heart cells in
vitro. To better understand the role TGF-[beta] might play as a paracrine
mediator of cardiac hypertrophy, the expression and secretion of TGF-[beta]
was examined. Neonatal cardiac fibroblasts in vitro secreted latent TGF-
[beta]1+TGF-[beta]2 as high as 15 ng/106 cells. Angiotensin II (AII) and
norepinephrine (NE) each augmented up to three fold the expression and
secretion of latent TGF-[beta]1 and TGF-[beta]2, and also induced a shift in
isoform predominance from [beta]1 to [beta]2. To understand the potential role
of NE and AII enhanced secretion of TGF-[beta], the effects of recombinant
TGF-[beta] and of NE and AII on cell growth were studied. Each individually
produced hypertrophic growth of neonatal cardiocytes and hyperplastic growth
of cardiac fibroblasts. Paradoxically, the combination of NE and AII at
intermediate and high concentrations resulted in less TGF-[beta] secretion
(compared to either agent alone) and to hypertrophic growth of fibroblasts.
These results suggest that the growth promoting effects of AII and NE may in
part be mediated via a paracrine stimulation of TGF-[beta] secretion. However,
the cumulative influences of multiple agents on heart cell growth is complex.
Received 22 June 1994; accepted in final form 2 November 1994
APS Manuscript Number C0352-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1994 The American Physiological Society.
Published in APStracts on 27 February 1995.