Nicotine-induced smooth muscle cell proliferation is mediated through bFGF and TGF-beta 1.
BACKGROUND
Cigarette smoking influences and enhances the development of atherosclerosis. We investigated if nicotine, an important constituent of cigarette smoking, has a stimulatory effect on bovine smooth muscle cell proliferation in vitro through the mediation of bFGF and TGF-beta 1.


METHODS
Bovine aortic smooth muscle cells (SMC) were stimulated with (-)-nicotine at various concentrations ranging from 6 x 10(-4) mol/L to 6 x 10(-8) mol/L. SMC viability and count were assessed. The presence of bFGF and TGF-beta 1 in serum-free conditioned media was determined by the inhibition antibody-binding assay, and the mitogenic activity of (-)-nicotine on SMC was analyzed by the 3H-thymidine uptake. Polymerase chain reaction was used to study the expression of bFGF and TGF-beta 1.


RESULTS
The bFGF release after (-)-nicotine stimulation was greater than in the controls, whereas TGF-beta 1 release was lower. The greatest mitogenic activity was found at a (-)-nicotine concentration of 6 x 10(-6) mol/L. The addition of monoclonal antibody anti-bFGF decreased the 3H-thymidine uptake of SMC exposed to (-)-nicotine, whereas the addition of monoclonal antibody anti-TGF-beta 1 increased the 3H-thymidine uptake of stimulated SMC. bFGF mRNA expression was significantly higher in SMC exposed to (-)-nicotine than in the controls, but TGF-beta 1 mRNA expression was significantly lower in SMC exposed to 6 x 10(-6) mol/L (-)-nicotine than in SMC treated with the other concentrations of (-)-nicotine and in controls.


CONCLUSIONS
Nicotine is a potent regulator of bFGF and TGF-beta 1 production and release by aortic SMC, and it seems to play an important role in the development and progression of atherosclerosis and neointimal fibrous hyperplasia.
Cucina
A
A
First Department of Surgery, University of Rome La Sapienza, Italy.
Sapienza
P
P
Corvino
V
V
Borrelli
V
V
Mariani
V
V
Randone
B
B
Santoro D'Angelo
L
L
Cavallaro
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001161:Arteriosclerosis / Q000209:etiology; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000502:physiology*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects*; D009538:Nicotine / Q000633:toxicity*; D012333:RNA, Messenger / Q000032:analysis; D012907:Smoking / Q000009:adverse effects; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*
D000911:Antibodies, Monoclonal; D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D009538:Nicotine