title: Factor Xa acts as a PDGF-independent mitogen in human vascular smooth muscle cells.
abstract: This study investigates the mitogenic effect of the coagulation factor Xa in smooth muscle cells (SMC) from human saphenous vein and the procoagulant activity of these cells. Factor Xa elicited a concentration-dependent increase in [3H]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 concentration- and time-dependently. PDGF-neutralizing antibodies neither inhibited the increase in [3H]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. Exposure of SMC to recalcified plasma resulted in a significant thrombin generation 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.
authors.affiliation: Zentrum für Vaskuläre Biologie und Medizin Erfurt, Friedrich-Schiller-Universität Jena, Germany. bretschn@zmkh.ef.uni-jena.de
authors.forename: E
authors.initials: E
authors.lastname: Bretschneider
authors.forename: M
authors.initials: M
authors.lastname: Braun
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: M
authors.initials: M
authors.lastname: Wittpoth
authors.forename: E
authors.initials: E
authors.lastname: Glusa
authors.forename: K
authors.initials: K
authors.lastname: Schrör
mesh_terms: D001777:Blood Coagulation; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D004789:Enzyme Activation; D015951:Factor Xa / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D007700:Kinetics; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D008934:Mitogens; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D012501:Saphenous Vein / Q000166:cytology; D013917:Thrombin / Q000378:metabolism; D013936:Thymidine / Q000493:pharmacokinetics; D014316:Tritium
chemical_list: D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D014316:Tritium; D020929:Mitogen-Activated Protein Kinase Kinases; D013917:Thrombin; D015951:Factor Xa; D013936:Thymidine