Nicotine-induced smooth muscle cell proliferation is mediated through bFGFand TGF-beta(1)

Background. Cigarette smoking influences and enhances the development of at herosclerosis. We investigated if nicotine, an important constituent of cig arette smoking, has a stimulatory effect on bovine smooth muscle cell proli feration in vitro through the mediation of bFGF and TGF-beta(1). Methods. Bovine aortic smooth muscle cells (SMC) were stimulated with (-)-n icotine 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 T GF-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 H-3-thymidine uptake. Polymerase chain reaction was use d to study the expression of bFGF and TGF-beta(1). Results. The bFGF release after (-)-nicotine stimulation was greater than i n the controls, whereas TGF-beta(1) release was lower. The greatest mitogen ic activity was found at a (-)-nicotine concentration of 6 x 10(-6) mol/L. The addition of monoclonal antibody anti-bFGF decreased the H-3-thymidine u ptake of SMC exposed to (-)-nicotine, whereas the addition of monoclonal an tibody anti-TGF-beta(1) increased the H-3-thymidine uptake of stimulated SM C. 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) product ion and release by aortic SMC, and it seems to play an important role in th e development and progression of atherosclerosis and neointimal fibrous hyp erplasia.