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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
1   From the Zentrum für Vaskuläre Biologie und Medizin Erfurt, Friedrich-Schiller-Universität Jena, Germany
,
Marina Braun
2   Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany
,
Annett Fischer
1   From the Zentrum für Vaskuläre Biologie und Medizin Erfurt, Friedrich-Schiller-Universität Jena, Germany
,
Michael Wittpoth
2   Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany
,
Erika Glusa
1   From the Zentrum für Vaskuläre Biologie und Medizin Erfurt, Friedrich-Schiller-Universität Jena, Germany
,
Karsten Schrör
2   Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany
› Author AffiliationsThis study was supported by the Verbund für Klinische Forschung of the Friedrich-Schiller-Universität Jena (FS 5, Projekt 4) and by the Deutsche Forschungsgemeinschaft (Schr 194/10-3). The authors wish to thank Dr. S. Kunitada (Daiichi Pharmaceuticals, Tokyo, Japan) for the generous supply with DX-9065a, Dr. J. Stürzebecher and Dr. Dagmar Prasa for their support in measuring thrombin generation. The authors are also grateful to Marlies Laube and Christine Machunsky for competent technical assistance and to Erika Lohmann for secretarial help.
Further Information

Publication History

Received 22 February 2000

Accepted after resubmission 17 April 2000

Publication Date:
14 December 2017 (online)

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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
 

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