Factor Xa Acts as a PDGF-Independent Mitogen in Human Vascular Smooth Muscle Cells

Ellen Bretschneider; Marina Braun; Annett Fischer; Michael Wittpoth; Erika Glusa; Karsten Schrör

doi:10.1055/s-0037-1614051

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2000; 84(03): 499-505
DOI: 10.1055/s-0037-1614051

Commentary

Schattauer GmbH

Factor Xa Acts as a PDGF-Independent Mitogen in Human Vascular Smooth Muscle Cells

Ellen Bretschneider

¹From the Zentrum für Vaskuläre Biologie und Medizin Erfurt, Friedrich-Schiller-Universität Jena, Germany

,

Marina Braun

²Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany

,

Annett Fischer

¹From the Zentrum für Vaskuläre Biologie und Medizin Erfurt, Friedrich-Schiller-Universität Jena, Germany

,

Michael Wittpoth

²Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany

,

Erika Glusa

¹From the Zentrum für Vaskuläre Biologie und Medizin Erfurt, Friedrich-Schiller-Universität Jena, Germany

,

Karsten Schrör

²Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany

› Author Affiliations

Abstract

Summary

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 concentrationdependent 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.

Key words

Factor Xa - vascular smooth muscle cells - mitogenesis - thrombin generation

Full Text

References

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