Interaction of thrombin with heparin cofactor II and antithrombin III on prostacyclin production by cultured endothelial cells.
To investigate the physiologic function of heparin cofactor II (HCII), endothelial cells from human umbilical vein were incubated in vitro for 20 min with 0.5 NIH U/ml thrombin in the presence of HCII or antithrombin III (ATIII), and prostacyclin production determined by radioimmunoassay for 6-keto-prostaglandin F1 alpha, the stable metabolite of prostacyclin. Although ATIII at 20 mInh.U/ml slightly but significantly inhibited thrombin-induced prostacyclin production, neither unfractionated heparin (UFH) nor low molecular weight heparin (LMWH) at 1 U/ml accelerated the inhibitory effect of ATIII. HCII at 10 and 20 mInh.U/ml did not decrease thrombin stimulation of prostacyclin production in the presence or absence of UFH or LMWH. However, HCII caused a marked decrease in the thrombin-stimulated prostacyclin prostacyclin production in the presence of 2 mg/ml dermatan sulfate (DS). The significant inhibition by HCII occurred when the DS concentrations were 0.2 microgram/ml and higher. From these results we suggest that HCII may prevent a prostacyclin-induced inhibition of platelet aggregation for hemostasis when plasma is exposed to vascular smooth muscle cells or fibroblasts which synthesize a significant amount of DS.
Kaji
T
T
Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Itoh
F
F
Hayakawa
Y
Y
Oguma
Y
Y
Sakuragawa
N
N
D000990:Antithrombin III / Q000494:pharmacology*; D002478:Cells, Cultured; D003871:Dermatan Sulfate / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D006493:Heparin / Q000494:pharmacology; D015844:Heparin Cofactor II / Q000494:pharmacology*; D006801:Humans; D013917:Thrombin / Q000494:pharmacology*
D003871:Dermatan Sulfate; D015844:Heparin Cofactor II; D000990:Antithrombin III; D006493:Heparin; D011464:Epoprostenol; D013917:Thrombin