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.