Effects of Rapamycin on Growth Factor-Stimulated Vascular Smooth Muscle Cell Dna Synthesis Inhibition of Basic Fibroblast Growth Factor and Platelet-Derived Growth Factor Action and Antagonism of Rapamycin by Fk506

Rapamycin (RPM) is a potent and effective immuno-suppressant which we have shown previously to inhibit intimai thickening in rat allograft and balloon-injured arteries. In this report, we have examined the effects of RPM on growth factor-induced vascular smooth muscle cell (VSMC) DNA synthesis. RPM potently inhibited platelet-derived growth factor (PDGF) (IC50=5×10-9 M) and basic fibroblast growth factor (bFGF) (IC50=8×10-10 M)-induced VSMC DNA synthesis. In contrast, only the highest concentrations of FK506 and CsA significantly altered PDGF- or bFGF-induced VSMC DNA synthesis. Addition of RPM (10-9 M) at as late as 46 hr after growth factor addition still effectively suppressed bFGF- or PDGF-induced DNA synthesis by 76% and 54%, respectively. The extent of the antagonism of RPM's inhibition of bFGF-induced VSMC DNA synthesis by FK506 was inversely proportional to RPM concentration and directly proportional to FK506 concentration.