Effects of a low molecular weight heparin, bemiparin, and unfractionated heparin on hemostatic properties of endothelium.
Human endothelial cells synthesize and secrete a variety of molecules involved in fibrinolysis and coagulation. The effects of a low molecular weight heparin, Bemiparin, and unfractionated heparin (UFH) were compared on plasminogen activator inhibitor-1 (PAI-1), tissue-plasminogen activator (t-PA), tissue factor (TF), tissue factor pathway inhibitor (TFPI) release, and PAI-1 gene expression by human umbilical vein endothelial cells (HUVEC). Cell cultures were supplemented with Bemiparin or UFH at 1 or 10 U/mL. Culture media samples were obtained before the addition of the drugs and 2, 6, and 24 hours afterward to measure the antigen levels of TF, TFPI, t-PA, and PAI-1. RNA was obtained to study the endothelial expression of PAI-1 by reverse transcriptase-polymerase chain reaction (RT-PCR). Bemiparin at 1 U/mL resulted in a decreased messenger RNA (mRNA) PAI-1 expression, which remained unaltered when UFH had been added. PAI-1 levels increased after the cultures had been supplemented with either Bemiparin or UFH at both doses. UFH induced an increase in t-PA either at 1 or 10 U/mL. Both doses of UFH, but not Bemiparin, induced an important increase in TF secretion. An increase in the TFPI levels was seen with UFH at 1 U/mL. The decrease in PAI-1 gene expression observed with a therapeutic dose of Bemiparin might confer this drug interesting profibrinolytic properties. The fact that Bemiparin, in contrast with UFH, does not induce an increase in TF could give this drug another positive feature.
Pérez-Ruiz
Ana
A
Haemostasis and Thrombosis Research Unit, School of Medicine, University of Navarra, Pamplona, Spain.
Montes
Ramón
R
Carrasco
Pilar
P
Rocha
Eduardo
E
D000925:Anticoagulants / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005342:Fibrinolysis; D005786:Gene Expression Regulation / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006801:Humans; D008074:Lipoproteins / Q000032:analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013925:Thromboplastin / Q000032:analysis; D010959:Tissue Plasminogen Activator / Q000032:analysis / Q000378:metabolism; D014471:Umbilical Veins
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D008074:Lipoproteins; D017395:Plasminogen Activator Inhibitor 1; C051928:lipoprotein-associated coagulation inhibitor; D006493:Heparin; D013925:Thromboplastin; D010959:Tissue Plasminogen Activator; C411345:bemiparin