Thrombin signal transduction of the fibrinolytic system in human adult venous endothelium in vitro.
Thrombin can regulate the-fibrinolytic system by increasing the endothelial production of both tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1). The thrombin receptor transducts signals through the GTP-binding protein system, the classical pathway being the Galpha q-protein. The purpose of the present study was to examine the roles of Galpha i-protein and tyrosine kinases in the thrombin signal transduction of t-PA and PAI-1 production from human adult vein endothelial cells (HAVEC). t-PA and PAI-1 antigen were analysed in conditioned medium from cultured HAVEC after 16 h incubation. Data are expressed as percentages of basal release (100%), means +/- 95% confidence intervals. Thrombin increased t-PA and PAI-1 production (234 +/- 42% and 211 +/- 42%, respectively). Pertussis toxin (PTX) (inhibiting Galpha i-pathway) reduced basal PAI-1 (66 +/- 8%), but had only a weak influence on basal t-PA production. Pertussis toxin and genistein (inhibiting tyrosine kinase) significantly reduced the thrombin induction of both t-PA and PAI-1 (PTX: 142 +/- 23% and 146 +/- 19%, respectively, genistein: 156 +/- 42% and 76 +/- 24%, respectively). The present study demonstrated that thrombin can increase the production of t-PA and PAI-1 by transducting signals through the Galpha i and tyrosine kinase pathway, in addition to the Galpha q/protein kinase C pathway as has been found previously.
Rydholm
H E
HE
Department of Surgery, Sahlgrenska University Hospital Ostra, Göteborg University, Sweden.
Falk
P
P
Eriksson
E
E
Risberg
B
B
D000328:Adult; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005342:Fibrinolysis; D019204:GTP-Binding Proteins / Q000502:physiology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D015398:Signal Transduction; D013917:Thrombin / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis
D017395:Plasminogen Activator Inhibitor 1; D019833:Genistein; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D019204:GTP-Binding Proteins