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

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...

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Detalles Bibliográficos
Autores: Orbe-Lopategui, J. (Josune)|||/items/033ea7ef-1eff-418a-9fc4-1e2d3498d726, Montes, R. (Ramón)|||/items/8f33031a-c4c2-48c3-beb6-0177898ba38d, Zabalegui, N. (Natalia)|||/items/f09ce17d-3127-4609-881f-c8ae3c244607, Perez-Ruiz, A. (Ana)|||/items/fbeb9d68-51d3-4c79-83dd-80a487d8b5a4, Páramo-Fernández, J.A. (José Antonio)|||/items/8c56baa6-2a43-4836-b91b-4eed15be3c96
Tipo de recurso: artículo
Fecha de publicación:1999
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/22262
Acceso en línea:https://hdl.handle.net/10171/22262
Access Level:acceso abierto
Palabra clave:Heparin
mRNA
Hirudin
Endotoxin
PAI-1
HUVEC
Descripción
Sumario: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.