Plasmin-mediated fibroblast growth factor-2 mobilisation supports smooth muscle cell proliferation in human saphenous vein

The focus of this study was identification of the contribution of the plasm inogen activator-plasmin system to smooth muscle cell proliferation and mig ration in human saphenous vein. Segments of human saphenous vein were grown in organ culture for up to 14 days. Smooth muscle cell proliferation and, migration were measured by incubating vein segments in bromodeoxyuridine, a nd smooth muscle cell death was detected by in situ end-labelling. Tissue-t ype (tPA): and urokinase-type (uPA) plasminogen activator enzymic activitie s were detectable in cultured saphenous vein segments, and were concentrate d in focal zones. Inhibition of plasmin activity with alpha -N-acetyl-L-lys ine methyl ester (NALME) or of uPA activity with a neutralising antibody ca used significant decreases in smooth muscle cell proliferation in the media and the intima, but no significant changes in smooth muscle cell migration . Intimal thickness was also significantly decreased. Incubation with plasm inogen or plasmin caused fibroblast growth factor-2 (FGF2) to be released i nto the medium. Addition of FGF2 to segments cultured with NALME reversed t he inhibition of smooth muscle cell proliferation, and blocking the activit y of FGF2 with a neutralising antibody caused a significant decrease in med ial smooth muscle cell proliferation. These data suggest that plasmin mobil ises. FGF2 bound to the extracellular matrix of human saphenous vein, so th at it can support smooth muscle cell proliferation and intimal thickening. Copyright (C) 2001 S. Karger AG, Basel.