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Thromb Haemost 1987; 57(02): 148-153
DOI: 10.1055/s-0038-1651084
Original Article
Schattauer GmbH Stuttgart

Effect of Thrombin on the Production of Plasminogen Activators and PA Inhibitor-1 by Human Foreskin Microvascular Endothelial Cells

Victor W M Van Hinsbergh
The TNO Gaubius Institute for Cardiovascular Research, Leiden, The Netherlands
,
Erik D Sprengers
The TNO Gaubius Institute for Cardiovascular Research, Leiden, The Netherlands
,
Teake Kooistra
The TNO Gaubius Institute for Cardiovascular Research, Leiden, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 04 September 1986

Accepted after revision 12 December 1986

Publication Date:
28 June 2018 (online)

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Summary

Human foreskin microvascular endothelial cells synthesize and release tissue-type plasminogen activator (t-PA) in similar amounts as do endothelial cells from umbilical cord artery and vein. Human thrombin increases the production of t-PA by these cells, which could be visualized from 8 h after addition of 0.1-5 units/ml thrombin by fibrin autography after SDS polyacrylamide gel electrophoresis of the endothelial cell conditioned media. Thrombin also increased the secretion of t-PA antigen. Together with t-PA, human microvascular cells release urokinasetype plasminogen activator (u-PA) antigen and endothelial cell-type PA inhibitor, PA inhibitor-1, which were both demonstrated by specific immunoprécipitation from radiolabeled endothelial cell conditioned medium. Thrombin increases the release of u-PA antigen, but no u-PA activity could be demonstrated. Thrombin induced a two-fold stimulation of the synthesis and secretion of PA inhibitor-1 antigen. At 0.1 unit/ml thrombin also an increase in PA inhibitor activity was found. At high concentrations of thrombin a decrease of PA inhibitor activity was found, due to the conversion of the active 46 kD PA inhibitor-1 into a 42 kD product without PA inhibitor activity. Our data indicate that interaction of thrombin with microvascular endothelial cells will shift the balance between t-PA, u-PA and PA inhibitor-1, and thus affects the regulation of fibrinolysis.

Keywords

Microvascular endothelial cells - Thrombin - Plasminogen activator inhibitor - Plasminogen activators
 

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