THE INHIBITORY EFFECT OF HEPARIN FOR VASCULAR SMOOTH-MUSCLE CELL-PROLIFERATION OR MIGRATION IS NOT MEDIATED BY U-PA AND T-PA

Previous works suggest the interesting possibility of an effect of hep arin on vascular smooth muscle cell (SMC) replication and migration vi a a selective inhibition of the expression of t-PA and u-PA both of wh ich may play major roles during intimal hyperplasia following endothel ial injury. The present study was undertaken to evaluate in vitro the effect of heparin on the growth and migration of aortic SMC isolated f rom transgenic mice showing single inactivations of the t-PA and u-PA genes comparatively to SMC isolated from control mice. With regard to serum-induced proliferation and migration, all cell types showed simil ar responses. On control cells, heparin inhibited in a dose-dependent manner the expression of both t-PA and u-PA protein and mRNA. Heparin however, similarly affected the mitogenic and chemotactic activity of FCS for SMC isolated from control, t-PA or u-PA-deficient mice therefo re showing that heparin inhibits FCS-induced SMC proliferation via mec hanism(s) other than single inhibition of t-PA or u-PA expression by s mooth muscle cells. (C) 1997 Elsevier Science Ltd.