Platelet-activating factor (PAF) is not an essential component of the cascade leading to smooth muscle cell proliferation following vascular injury.
In order to evaluate the relative importance platelet-activating factor (PAF) in the proliferative process leading to restenosis, the effect of SR 27417, a novel highly potent PAF receptor antagonist, on PAF-induced rabbit aortic smooth muscle cell (SMC) proliferation and intimal hyperplasia in rabbit carotid arteries subjected to air-drying endothelial injury was investigated. When added to low concentrations of foetal calf serum, PAF showed a dose-dependent mitogenic effect with regard 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 day, p.o.) abrogated PAF-induced platelet aggregation ex vivo but did not affect the development of intimal thickening, therefore showing that PAF is not an essential component of the cascade leading to restenosis following vascular injury.
Herbert
J M
JM
Haemobiology Research Department, Sanofi Recherche, Toulouse, France.
Laplace
M C
MC
Mares
A M
AM
Dol
F
F
D000818:Animals; D001011:Aorta; D002455:Cell Division / Q000187:drug effects; D004730:Endothelium, Vascular / Q000473:pathology; D006965:Hyperplasia; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D013844:Thiazoles / Q000494:pharmacology; D014652:Vascular Diseases / Q000209:etiology / Q000473:pathology*
D010972:Platelet Activating Factor; D013844:Thiazoles; C071317:Foropafant