Nicotine-induced smooth muscle cell proliferation is mediated through bFGF and TGF-β1

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 (3)H-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 (3)H-thymidine uptake of SMC exposed to (-)-nicotine, whereas the addition of monoclonal antibody anti-TGF-beta(1) increased the (3)H-thymidine uptake of stimulated SMC. bFGF 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 (-0-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.