title: Interaction of thrombin with heparin cofactor II and antithrombin III on prostacyclin production by cultured endothelial cells.
abstract: 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.
authors.affiliation: Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kaji
authors.forename: F
authors.initials: F
authors.lastname: Itoh
authors.forename: Y
authors.initials: Y
authors.lastname: Hayakawa
authors.forename: Y
authors.initials: Y
authors.lastname: Oguma
authors.forename: N
authors.initials: N
authors.lastname: Sakuragawa
mesh_terms: 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*
chemical_list: D003871:Dermatan Sulfate; D015844:Heparin Cofactor II; D000990:Antithrombin III; D006493:Heparin; D011464:Epoprostenol; D013917:Thrombin