PLATELET-ACTIVATING-FACTOR (PAF) IS NOT AN ESSENTIAL COMPONENT OF THECASCADE LEADING TO SMOOTH-MUSCLE CELL-PROLIFERATION FOLLOWING VASCULAR INJURY

In order to evaluate the relative importance platelet-activating facto r (PAF) in the proliferative process leading to restenosis, the effect of SR 27417, a novel highly potent PAF receptor antagonist, on PAF-in duced rabbit aortic smooth muscle cell (SMC) proliferation and intimal hyperplasia in rabbit carotid arteries subjected to air-drying endoth elial injury was investigated. When added to low concentrations of foe tal calf serum, PAF showed a dose-dependent mitogenic effect with rega rd to rabbit arterial SMC. SR 27417 inhibited PAF-induced SMC growth ( IC50=2.4+/-0.4 nM) but remained without effect on the mitogenic effect of foetal calf serum. A 16 day treatment of SR 27417 (10 mg/kg per da y, p.o.) abrogated PAF-induced platelet aggregation ex vivo but did no t affect the development of intimal thickening, therefore showing that PAF is not an essential component of the cascade leading to restenosi s following vascular injury.