Evidence that heparin but not hirudin reduces PAI-1 expression in cultured human endothelial cells
Orbe J, Montes R, Zabalegui N, Pérez-Ruiz A, Páramo JA.
Laboratory of Vascular Biology and Thrombosis, Haematology Service, School of Medicine, University of Navarra, Pamplona, Spain.
Magazine: Thrombosis Research
Date: May 1, 1999Haematology and Hameotherapy
Heparin and other antithrombotic drugs besides their anticoagulant action could have a profibrinolytic effect. We have analyzed the effect of unfractionated heparin (UFH) and hirudin on PAI-1 gene expression in human umbilical vein endothelial cells (HUVEC). Cells were stimulated with UFH (1 and 10 IU/ml) and hirudin (20 and 100 TIU/ml).
Samples were obtained before and 2, 6, and 24 hours after stimulation. mRNA analysis was conducted by reverse transcription followed by polymerase chain reaction, and PAI-1 antigen was determined by ELISA. Addition of UFH (10 IU/ml) to HUVEC resulted in a decrease of PAI-1 mRNA at 6 hours (40% reduction) and 24 hours (60% reduction) and PAI-1 antigen. Hirudin, however, did not modify significantly the PAI-1 mRNA nor the inhibitor secretion. The addition of UFH (10 or 100 IU/ml) to endotoxin-stimulated HUVEC also reduced the increased PAI-1 mRNA and antigen secretion (45%), whereas no effect could be observed with hirudin.
Our results suggest that UFH, but not hirudin, by reducing the endothelial expression of PAI-1 might have a profibrinolytic effect.
CITATION Thromb Res. 1999 May 1;94(3):137-45
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