Evidence that heparin but not hirudin reduces PAI-1 expression in culturedhuman endothelial cells

Heparin and other antithrombotic drugs besides their anticoagulant action c ould have a profibrinolytic effect. We have analyzed the effect of unfracti onated heparin (UFH) and hirudin on PAI-1 gene expression in human umbilica l 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 decr ease 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 antig en secretion (45%), whereas no effect could be observed with hirudin. Our r esults suggest that UFH, but not hirudin, by reducing the endothelial expre ssion of PAI-1 might have a profibrinolytic effect. (C) 1999 Elsevier Scien ce Ltd. All rights reserved.