Nicotine induces platelet-derived growth factor release and cytoskeletal alteration in aortic smooth muscle cells

Background, Cigarette smoking is implicated in atherosclerotic plaque forma tion, but the role of nicotine in this process is not completely understood . The release of platelet-derived growth factor (PDGF) by the bovine aortic smooth muscle cell (SMC) after nicotine administration at a concentration similar to that ingested by active and passive smokers and the role of PDGF in SMC cytoskeleton modification were studied. Methods. SMC, harvested with enzymatic digestion from calf aorta, were stim ulated in a serum-free medium for 72 hours with (-)-nicotine (from 6 x 10(4 ) mol/L to 6 x 10(8) mol/L). The release of PDGF was assessed by inhibition antibody-binding assay and confirmed by Western blotting. Mitogenic activi ty of nicotine on SMCs was also determined. The SMC cytoskeleton was studie d with specific antibodies anti-alpha-actin fibers, anti-vimentin, and anti -beta-tubulin, and the modification induced by PDGF was assessed by blockin g PDGF activity with specific antibodies. Results. The greatest PDGF release (1.24 +/- 0.14 ng/10(4) cells vs control 0.43 +/- 0.07 ng/10(4) cells) was noted at a (-)-nicotine concentration of 6 x 10(7) mol/L (P < .001). The addition of monoclonal antibody anti-PDGF decreased the tritiated thymidine uptake of SMCs exposed to (-)-nicotine co mpared with the control (29% vs 5% - P < .001). SMCs exposed to (-)-nicotin e concentration of 6 x 10(7) mol/L and 6 x 10(8) mol/L had a significant al teration in the expression of alpha-actin fibers, vimentin, and beta-tubuli n compared with central. The administration of antibody anti-PDGF in the cu lture medium reversed cytoskeletal alteration. Conclusions. Nicotine enhanced the release of platelet-derived growth, whic h in turn caused an alteration in cytoskeletal organization.