Factor Xa acts as a PDGF-independent mitogen in human vascular smooth muscle cells

This study investigates the mitogenic effect of the coagulation factor Xa i n smooth muscle cells (SMC) From human saphenous vein and the procoagulant activity of these cells. Factor Xa elicited a concentration-dependent incre ase in [H-3]thymidine incorporation. This mitogenic effect of factor Xa was inhibited by DX-9065a and BABCH, indicating the requirement of proteolytic activity of the enzyme. Factor Xa activated the MAP kinases ERK1/2 concent ration- and time-dependently. PDGF-neutralizing antibodies neither inhibite d the increase in [H-3]thymidine incorporation nor ERK-1/2 phosphorylation in factor Xa-stimulated cells, suggesting that factor Xa-induced signaling and mitogenic activity in human venous SMC are independent of PDGF, Exposur e of SMC to recalcified plasma resulted in a significant thrombin generatio n which was inhibited by anti-tissue factor antibody, tissue factor pathway inhibitor, inactivated factor VIIa and DX-9065a. These data indicate that interaction of SMC with the clotting system may contribute to venous graft disease, i.e, thrombus formation and intimal hyperplasia.