Evidence that heparin but not hirudin reduces PAI-1 expression in cultured human endothelial cells
Research article published in Thrombosis research (1999)
Abstract
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.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
Heparin and other antithrombotic drugs besides their anticoagulant action could have a profibrinolytic effect.
Why This Matters for Hirudotherapy
In cultured human umbilical vein endothelial cells, this study compared unfractionated heparin and hirudin and found that heparin (10 IU/ml) reduced PAI-1 mRNA by about 40% at 6 hours and 60% at 24 hours and lowered PAI-1 antigen, including in endotoxin-stimulated cells, whereas hirudin produced no significant change in PAI-1 expression or secretion, suggesting heparin but not hirudin may have a profibrinolytic effect through this pathway. For hirudotherapy this is a useful mechanistic boundary marker: it indicates that hirudin's action is a relatively specific direct thrombin inhibition and does not, unlike heparin, downregulate the fibrinolysis inhibitor PAI-1 in endothelium, refining how the leech-derived anticoagulant differs pharmacologically from heparin. The caveat is that this is an in vitro cell-culture study of one molecular endpoint; it characterizes a difference in mechanism rather than any clinical outcome, and a negative result for hirudin on PAI-1 says nothing about its established anticoagulant utility.
Citation
Evidence that heparin but not hirudin reduces PAI-1 expression in cultured human endothelial cells
Orbe J et al. · Thrombosis research, 1999
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