Heparin cofactor II inhibits thrombin-stimulated release of tissue plasminogen activator from cultured human endothelial cells in the presence of dermatan sulfate

Abstract

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 HCII or antithrombin III (ATIII) combined with or without thrombin. Although ATIII significantly inhibited thrombin-induced increase in tissue plasminogen activator antigen (t-PA:Ag) release, HCII did not exhibit such a suppressive effect. In contrast, in the presence of dermatan sulfate, HCII inhibited thrombin stimulation of t-PA:Ag release more strongly than ATIII 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 HCII and dermatan sulfate. Comparatively high concentrations of HCII 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 HCII 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.