Heparin cofactor II inhibits thrombin-stimulated release of tissue plasminogen activator from cultured human endothelial cells in the presence of dermatan sulfate.
To investigate the involvement of heparin cofactor II (HC II) in fibrinolytic system, endothelial cells from human umbilical vein were cultured in the presence of HC II or antithrombin III (AT III) combined with or without thrombin. Although AT III significantly inhibited thrombin-induced increase in tissue plasminogen activator antigen (t-PA:Ag) release, HC II did not exhibit such a suppressive effect. In contrast, in the presence of dermatan sulfate, HC II inhibited thrombin stimulation of t-PA:Ag release more strongly than AT III did. The release of plasminogen activator inhibitor-1 antigen (PAI-1:Ag) was also stimulated by thrombin; this stimulation was inhibited only by the combination of HC II and dermatan sulfate. Comparatively high concentrations of HC II significantly suppressed thrombin stimulation of t-PA:Ag and PAI-1:Ag release but did not cause an obvious change of both release in the absence of thrombin. Based on these results, it was suggested that HC II may inhibit an increase in fibrinolytic activity mediated by thrombin-stimulated endothelial cells in the liquid phase through a suppression of thrombin stimulation of t-PA:Ag release, when plasma is exposed to vascular smooth muscle cells or fibroblasts which synthesize a significant amount of dermatan sulfate.
Kaji
T
T
Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Ejiri
N
N
Hayakawa
Y
Y
Hayashi
T
T
Sakuragawa
N
N
D000990:Antithrombin III / Q000494:pharmacology; D002478:Cells, Cultured; D003871:Dermatan Sulfate / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015844:Heparin Cofactor II / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D015849:Plasminogen Inactivators / Q000276:immunology / Q000378:metabolism; D013917:Thrombin / Q000037:antagonists & inhibitors*; D010959:Tissue Plasminogen Activator / Q000276:immunology / Q000378:metabolism*
D015849:Plasminogen Inactivators; D003871:Dermatan Sulfate; D015844:Heparin Cofactor II; D000990:Antithrombin III; D013917:Thrombin; D010959:Tissue Plasminogen Activator