Regulation of baboon arterial smooth muscle cell plasminogen activators by heparin and growth factors

In addition to fibrinolysis, plasminogen activators may be involved in other processes relevant to atherogenesis such as smooth muscle cell migration, proliferation and extracellular matrix remodeling. Because mitogens such as basic fibroblast growth factor (bFGF) and platelet derived growth factor (PDGF) are positive regulatory factors and heparin is a negative regulatory factor for smooth muscle cell proliferation and migration, we have looked at the effects of these factors (plus serum and phorbol ester) on urokinase (uPA) and tissue plasminogen activator (tPA) of smooth muscle cells. PDGF, bFGF and serum increased tPA (serum > PDGF > FGF). Heparin inhibited the effect of serum, but not PDGF on tPA. Heparin actually increased the stimulatory effect of bFGF on tPA. Of interest, heparin was also able to inhibit mitogenesis mediated by serum, but not by PDGF or bFGF. Serum decreased and phorbol ester increased uPA, while PDGF and bFGF had no effect Heparin shifted uPA from the cell layer to the medium of serum or phorbol ester treated but not PDGF or bFGF treated cells. These data demonstrate that PDGF, bFGF and serum can differentially regulate smooth muscle cell plasminogen activators and that heparin can either increase or decrease levels of tPA or shift the localization of uPA depending on the mitogen used.