Modulation of smooth muscle proliferation in rat carotid artery by platelet-derived mediators and fibroblast growth factor-2.
Endothelial denuding injury to the rat carotid artery stimulates smooth muscle cell proliferation in the tunica media. Fibroblast growth factor-2 (FGF2) is responsible for a significant portion of this proliferation but other factors may contribute, particularly those released from adherent platelets. We therefore tested the effects of a range of platelet-derived factors. After filament injury, which minimises FGF2 release, the proliferation rate in thrombocytopaenic rats was decreased by 74% (P < 0.02). After balloon injury, antibody neutralisation of platelet-derived growth factor (PDGF) caused a 27% decrease in proliferation (P < 0.05), while inhibition of histamine H(1) receptors caused a 53% increase (P < 0.05). When filament injury was performed 1 h after FGF2 injection, the proliferation rate increased from 2.3+/-0.7 to 32.8+/-2.7% (P < 0.001), while filament injury alone caused a proliferation rate of only 18.3+/-2.9% (P < 0.01 versus filament plus FGF2). These data suggest that platelet-derived factors interact with FGF2 that is adsorbed to the vessel wall in the control of smooth muscle cell proliferation, and that the net effect of platelets is to stimulate smooth muscle cell proliferation. PDGF, but no other platelet agonist tested, contributes to that stimulation.
Lewis
C D
CD
Bristol Heart Institute, University of Bristol, Bristol BS2 8HW, UK.
Olson
N E
NE
Raines
E W
EW
Reidy
M A
MA
Jackson
C L
CL
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D020212:Carotid Artery Injuries / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004155:Diphenhydramine / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D008297:Male; D024510:Muscle Development / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013921:Thrombocytopenia / Q000503:physiopathology*
D000906:Antibodies; D006634:Histamine H1 Antagonists; D010982:Platelet-Derived Growth Factor; D016222:Fibroblast Growth Factor 2; D004155:Diphenhydramine