Nicotine reorganizes cytoskeleton of vascular endothelial cell through platelet-derived growth factor BB

Background. Cigarette smoking has been directly linked to atherosclerosis formation and vascular graft failures but the role of nicotine in these processes is not yet completely understood. We investigated the release of platelet-derived growth factor BB (PDGF BE) by the bovine aortic endothelial cell (EC) after nicotine administration at concentrations similar to those found in plasma of active and passive smokers and the role of PDGF BE, autocrinally released, in EC cytoskeletal modification. Methods. EC were stimulated in a serum-free medium for 72 h with (-)-nicotine (from 6 x 10(-4) to 6 x 10(-8) M). The release of PDGF BE was assessed by inhibition antibody-binding assay and confirmed by Western blotting. Mitogenic activity of nicotine on EC was also determined. The EC cytoskeleton was studied with specific antibodies anti-alpha-actin fibers and antivimentin and the modification induced by PDGF BE was assessed by blocking PDGF BE activity with specific antibodies. Results. The greatest PDGF BE release was noted at a (-)-nicotine concentration of 6 x 10(-6) M (P < 0.001). The addition of antibody anti-PDGF BE to EC exposed to (-)-nicotine decreased tritiated thymidine uptake by 20% (P < 0.001). EC exposed to (-)-nicotine concentrations of 6 x 10(-6) and 6 x 10(-8) M had a significant alteration in the expression of alpha-actin fibers and vimentin as compared with control. Administration of the antibody anti-PDGF BE in the culture medium reversed cytoskeletal alteration. Conclusions. Nicotine enhanced the release of PDGF BE by EC which in turn caused an alteration in cytoskeletal organization. (C) 2000 Academic Press.