Effect of unfractionated heparin and a low molecular weight heparin (enoxaparin) on coagulant activity of cultured human endothelial cells.
OBJECTIVE
Unfractionated heparin and low molecular weight heparins exert their anticoagulant effect by mobilizing tissue factor pathway inhibitor (TFPI) from the vascular endothelium into the blood circulation. We compared the influence of unfractionated heparin and enoxaparin on the anticoagulant function of cultured human endothelial cells.


METHODS
Monolayers of human umbilical vein endothelial cells were treated with 10 U/mL unfractionated heparin or enoxaparin for different periods of time (30min-48h). Endothelial cell procoagulant activity was determined in the cell lysates by a chromogenic assay. Endothelial cell tissue factor (TF) and released TFPI and von Willebrand factor (vWF) was determined.


RESULTS
In short periods of incubation (30min-2h), both heparins reduced endothelial cell procoagulant activity, the inhibition produced by unfractionated heparin being greater than that induced by enoxaparin (p<0.05). However, no variations were observed in TFPI and vWF release. With long periods of incubation (24-48h), both unfractionated heparin and enoxaparin significantly increased TFPI release (control vs. unfractionated heparin, p<0.05-0.001; control vs. enoxaparin, p<0.01-0.001) and also reduced the release of vWF in the culture medium, though no variations in endothelial cell procoagulant activity or TF content were observed.


CONCLUSIONS
Our findings show that unfractionated heparin and enoxaparin exert different kinds of effects on endothelial cells. With short incubation periods, procoagulant endothelial cell capacity was reduced to a greater extent by unfractionated heparin, while after longer periods of incubation enoxapain increased the anticoagulant activity of the endothelial cells to a greater degree than did unfractionated heparin.
Martinez-Sales
Vicenta
V
Centro de Investigación, La Fe University Hospital, Valencia, Spain. martinez_vicsal@gva.es
Vila
Virtudes
V
Réganon
Edelmiro
E
Oms
Javier Garcia
JG
Aznar
Justo
J
D000925:Anticoagulants / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D017984:Enoxaparin / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D000925:Anticoagulants; D017984:Enoxaparin; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D014841:von Willebrand Factor; D006493:Heparin; D013925:Thromboplastin