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Thromb Haemost 1993; 70(03): 469-474
DOI: 10.1055/s-0038-1649607
Original Article
Fibrinolysis
Schattauer GmbH Stuttgart

Thrombin Stimulates Expression of Tissue-Type Plasminogen Activator and Plasminogen Activator lnhibitor Type 1 in Cultured Human Vascular Smooth Muscle Cells

Johann Wojta
1   The Dept. Diagnostic Haematology, Royal Melbourne Hospital, Parkville, Victoria, Australia
2   The Dept. Medical Physiology, Laboratory for Clinical and Experimental Physiology, University of Vienna, Austria
,
Marisa Gallicchio
1   The Dept. Diagnostic Haematology, Royal Melbourne Hospital, Parkville, Victoria, Australia
,
Hans Zoellner
3   The Dept. Medicine, University of Melbourne, Parkville, Victoria, Australia
,
Peter Hufnagl
2   The Dept. Medical Physiology, Laboratory for Clinical and Experimental Physiology, University of Vienna, Austria
,
Karena Last
3   The Dept. Medicine, University of Melbourne, Parkville, Victoria, Australia
,
Enrico L Filonzi
3   The Dept. Medicine, University of Melbourne, Parkville, Victoria, Australia
,
Bernd R Binder
2   The Dept. Medical Physiology, Laboratory for Clinical and Experimental Physiology, University of Vienna, Austria
,
John A Hamilton
3   The Dept. Medicine, University of Melbourne, Parkville, Victoria, Australia
,
Katherine McGrath
1   The Dept. Diagnostic Haematology, Royal Melbourne Hospital, Parkville, Victoria, Australia
› Author Affiliations
Further Information

Publication History

Received 12 October 1992

Accepted after revision 10 March 1993

Publication Date:
05 July 2018 (online)

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Summary

The effect of thrombin on the fibrinolytic potential of human vascular smooth muscle cells (SMC) in culture was studied. SMC of different origin responded to thrombin treatment with a dose and time dependent increase in tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) levels in both cell lysates and conditioned media with maximum effects achieved at 10-20 IU/ml thrombin. PAI-1 antigen levels also increased in the extracellular matrix of thrombin treated SMC. PAI-2 levels in cell lysates of such SMC were not affected by thrombin. The effect was restricted to active thrombin, since DFP-thrombin and thrombin treated with hirudin showed no increasing effect on t-PA and PAI-1 levels in SMC.

Enzymatically active thrombin also caused a four-fold increase in specific PAI-1 mRNA and a three-fold increase in t-PA mRNA.

Furthermore we demonstrated the presence of high and low affinity binding sites for thrombin on the surface of SMC with a K D = 4.3 × 10−10 M and 9.0 × 104 sites per cell and a KD = 0.6 × 10−8 M and 5.8 × 105 sites per cell respectively.

Thrombin could come in contact with SMC in case of vascular injury or following gap formation between endothelial cells. Our data support the idea that besides its known proliferative effect for SMC, thrombin could also modulate their fibrinolytic system.

 

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