The addition of endothelial cell growth factor and heparin to human umbilical vein endothelial cell cultures decreases plasminogen activator inhibitor-1 expression.
Plasminogen activator inhibitor-1 (PAI-1) is a specific and rapid inhibitor of tissue plasminogen activator (tPA) and urokinase. Clinical studies suggest that PAI-1 may play a crucial role in the regulation of fibrinolysis. A number of factors modulate PAI-1 activity in endothelial cell culture, and the isolation of PAI-1 cDNA now allows study of PAI-1 regulation at the mRNA level. We examined the effect of endothelial cell growth factor (ECGF) and heparin on PAI-1 expression in human umbilical vein endothelial cell (HUVEC) culture. The addition of ECGF and heparin to HUVEC cultures results in a 3-10-fold decrease in the PAI-1 activity secreted into the conditioned media. This effect is mediated at the mRNA level. A decrease in PAI-1 is also seen with higher concentrations of ECGF alone, but is greatly enhanced by the addition of heparin. No significant change in tPA antigen or mRNA levels was observed.
D002478:Cells, Cultured; D003470:Culture Media; D004357:Drug Synergism; D016228:Endothelial Growth Factors; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006023:Glycoproteins / Q000096:biosynthesis*; D006133:Growth Substances / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors*; D015849:Plasminogen Inactivators; D012333:RNA, Messenger / Q000302:isolation & purification; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
D003470:Culture Media; D016228:Endothelial Growth Factors; D006023:Glycoproteins; D006133:Growth Substances; D015849:Plasminogen Inactivators; D012333:RNA, Messenger; D006493:Heparin; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator