Role of basic fibroblast growth factor in vascular lesion formation.
In the present study we investigated whether basic fibroblast growth factor (bFGF) plays a role in the proliferative response of smooth muscle cells (SMCs) to denuding injury. Rat carotid smooth muscle was found to express the mRNA for bFGF, and bFGF protein was found to be present in rat aorta by immunoblot analysis. Systemically administered bFGF was a potent mitogen for vascular SMCs in arteries denuded with a balloon catheter, increasing replication from 11.5% in controls to 54.8%. Denudation with a device (filament loop), which causes only minimal damage to medial SMCs, showed a similar increase in replication (1.3% versus 43.3%) after bFGF infusion. In unmanipulated vessels, however, SMCs were unresponsive to infused bFGF. Infusion of a "mitotoxin" (bFGF conjugated to saporin) caused a greater than 50% decrease in the number of viable SMCs in the arterial wall after balloon injury. Prolonged administration of bFGF (12 micrograms/day for 2 weeks) after balloon injury caused an approximately twofold increase in intimal thickening. These results show that bFGF, which is synthesized by the arterial wall, could be a potent mitogen for SMCs in vivo and suggest that any release of endogenous bFGF may be capable of stimulating SMC proliferation, which may subsequently lead to intimal lesion formation.
Lindner
V
V
Department of Pathology, School of Medicine, University of Washington, Seattle 98195.
Lappi
D A
DA
Baird
A
A
Majack
R A
RA
Reidy
M A
MA
D000818:Animals; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014652:Vascular Diseases / Q000503:physiopathology*
D008934:Mitogens; D016222:Fibroblast Growth Factor 2