Ancrod-formed fibrin stimulates prostacyclin production of human umbilical vein endothelial cells via de novo synthesis of cyclooxygenase.
Ancrod, a thrombin-like enzyme, has been used as defibrinogenating agent in prevention of venous thrombosis. This study showed ancrod in citrated plasma elevated 6-keto PGF1 alpha production of human umbilical vein endothelial cells; this increment of 6-keto PGF1 alpha was completely inhibited by Gly-Pro-Arg-Pro, an inhibitor of fibrin polymerization. The enhanced prostacyclin production, but not basal level of prostacyclin, was inhibited by actinomycin D and cycloheximide. In washed aspirin-pretreated cells, ancrod-formed fibrin induced restoration of prostacyclin production by a cycloheximide- and actinomycin D-sensitive process. Ancrod-formed fibrin stimulated synthesis of cyclooxygenase as probed by Western blotting and this enhancement was blocked by actinomycin D and cycloheximide. In conclusion, we first report that ancrod-formed fibrin stimulates prostacyclin production of human endothelial cells and this event is dependent on de novo synthesis of cyclooxygenase.
Chang
M C
MC
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
Wang
C Y
CY
Huang
T F
TF
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000721:Ancrod / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D005337:Fibrin / Q000096:biosynthesis / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D009842:Oligopeptides / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D014471:Umbilical Veins
D009842:Oligopeptides; D003609:Dactinomycin; D015121:6-Ketoprostaglandin F1 alpha; C034585:glycyl-prolyl-arginyl-proline; D005337:Fibrin; D003513:Cycloheximide; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D000721:Ancrod; D001241:Aspirin