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PDGF-AA, a potent mitogen for cardiac fibroblasts from adult rats.

Abstract：

:The heart responds to increased haemodynamic load with growth of the ventricles. The rise in ventricle mass is due to increasing mass of the myocytes and proliferation of fibroblasts and smooth muscle cells. The accompanying adaptation and remodelling of the interstitium, e.g. production and composition of the extracellular matrix proteins, determine a physiological or pathophysiological hypertrophy. Fibroblasts play a critical role in this process as the producers of extracellular matrix proteins. So far the growth factors involved are not well defined, and therefore we investigated the effect of platelet-derived growth factor (PDGF) isoforms on cellular proliferation of fibroblasts from adult rat hearts. Unlike other cell types of the cardiovascular system (e.g. smooth muscle cells), PDGF-AA has an extraordinarily high stimulatory effect on cell growth of these fibroblasts. It induces cell division to nearly the same extent and with the same kinetics as PDGF-BB as shown by cell number and flow cytometry. Cardiac fibroblasts do not express an unusually high number of PDGF alpha-receptors, (15300 PDGF alpha-receptors. 24800 PDGF beta-receptors per cell) which could explain this effect. The alpha-receptors display a lower and shorter autophosphorylation after stimulation with PDGF in comparison to the beta-receptors. The activation of the MAP kinase pathway is not different after stimulation with both PDGF isoforms. Interestingly, quiescent cardiac fibroblasts contain a preactivated p70S6-kinase. The specific drug rapamycin not only inhibits the p70S6-kinase activation but also PDGF induced cell proliferation for more than 50%. Because the p70S6-kinase activation is implicated in growth regulation in this cell system, the preactivation of this kinase is discussed to be a possible explanation for the enhanced growth effect of PDGF-AA.

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

Simm A,Nestler M,Hoppe V

doi

10.1006/jmcc.1996.0280

subject

Has Abstract

pub_date

1997-01-01 00:00:00

pages

357-68

issue

1

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(96)90280-1

journal_volume

29

pub_type

杂志文章

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