The effect of heparin and other glycosaminoglycans on levels of tissue plasminogen activator and plasminogen activator inhibitor in cultured human umbilical vein endothelial cells.
Human umbilical vein endothelial cells (HUVEC) were cultured in the presence of various glycosaminoglycans and the intracellular levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) measured by ELISA. 10 IU/ml heparin (90 micrograms/ml) brought about a significant (20-fold) increase in intracellular tPA levels over the 6-day culture period; intracellular PAI-1 levels were significantly decreased (by 60-70%) and culture growth rate promoted. The final cell density of heparin-containing cultures was 1.7 to 2.3 times greater than that of control cultures. Low molecular weight heparin (First International Standard) had similar effects but was less potent than unfractionated heparin. Chondroitin sulphate and heparan sulphate had no effect on tPA and PAI-1 levels but dermatan sulphate reduced PAI-1 significantly. The changes observed following exposure of HUVEC to heparin are consonant with the view that glycosaminoglycans may affect endothelial production of fibrinolytic components.
Marsh
N A
NA
School of Medicine, University of New South Wales, St George Hospital, Sydney, Australia.
Minter
A J
AJ
Chesterman
C N
CN
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D002809:Chondroitin Sulfates / Q000494:pharmacology; D003871:Dermatan Sulfate / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects*; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology; D006497:Heparan Sulfate / Q000494:pharmacology; D006801:Humans; D015849:Plasminogen Inactivators / Q000032:analysis*; D010959:Tissue Plasminogen Activator / Q000032:analysis*; D014471:Umbilical Veins
D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D006025:Glycosaminoglycans; D006493:Heparin; D006495:Heparin, Low-Molecular-Weight; D006497:Heparan Sulfate; D015849:Plasminogen Inactivators; D010959:Tissue Plasminogen Activator