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-β1. Methods: Bovine aortic smooth muscle cells (SMC) were stimulated with (-)-nicotine at various concentrations ranging from 6 × 10-4 mol/L to 6 × 10-8 mol/L. SMC viability and count were assessed. The presence of bFGF and TGF-β1 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-β1. Results: The bFGF release after (-)-nicotine stimulation was greater than in the controls, whereas TGF-β1 release was lower. The greatest mitogenic activity was found at a (-)-nicotine concentration of 6 × 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-β1 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-β1 mRNA expression was significantly lower in SMC exposed to 6 × 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-β1 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. (Surgery 2000:127:316-22.)