Inhibitory effect of heparin cofactor II on thrombin-stimulated prostacyclin production by cultured vascular smooth muscle cells.
We investigated the effect of heparin cofactor II (HCII) on thrombin-induced prostacyclin (PGI2) production by A10 cells, an established cell line of vascular smooth muscle cells from murine aorta. Confluent monolayers of A10 cells were incubated with 0.1 NIH U/ml of thrombin for 30 min in the presence of antithrombin III (ATIII) or HCII, and PGI2 production by the cells was measured by radioimmunoassay as 6-keto-prostaglandin F1a, the stable metabolite of PGI2. ATIII at 40 mInh.U/ml and more significantly inhibited thrombin-induced PGI2 production by A10 cells, but HCII at the same doses did only slightly. However, when A10 cells were preincubated with HCII for 30 min before exposure to thrombin, the PGI2 production was markedly inhibited. The medium conditioned by A10 cells for 30 min did not enhance the inhibitory effect of HCII on thrombin-induced PGI2 production by the cells. On the other hand, A10 cells synthesized both dermatan sulfate and heparan sulfate which are capable of activating HCII. From these results, it was suggested that HCII would be activated by glycosaminoglycans (GAGs) such as dermatan sulfate of the cell layers and could inhibit thrombin-induced PGI2 production. HCII may be a modulator of thrombin on the physiological functions of vascular smooth muscle cells, reacting to the cell surface GAGs.
Hayashi
T
T
Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Kaji
T
T
Hayakawa
Y
Y
Niiya
K
K
Sakamoto
M
M
Sakuragawa
N
N
D000990:Antithrombin III / Q000494:pharmacology*; D002460:Cell Line; D003871:Dermatan Sulfate / Q000032:analysis / Q000494:pharmacology; D011464:Epoprostenol / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry; D015844:Heparin Cofactor II / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000032:analysis / Q000494:pharmacology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011134:Polysaccharides / Q000737:chemistry
D000990:Antithrombin III; D003871:Dermatan Sulfate; D011464:Epoprostenol; D006023:Glycoproteins; D015844:Heparin Cofactor II; D006497:Heparan Sulfate; D011134:Polysaccharides