Calcium regulation of tissue plasminogen activator and plasminogen activator inhibitor-1 release from cultured human vascular endothelial cells.
Tissue plasminogen activator (t-PA) produced by vascular endothelial cells converts plasminogen to plasmin which degrades fibrin. Since t-PA activity is greatly potentiated in the presence of fibrin (1,2), the activator is implicated in intravascular fibrinolysis. On the other hand, endothelial cells also produce plasminogen activator inhibitor-1 (PAI-1) (3). The inhibitor associated with vascular endothelium rapidly inhibits t-PA, while that released into the liquid phase has a little anti-activator activity (4). However, clinical studies have shown that elevation of plasma PAI-1 level is a risk factor of thrombosis (5,6). It is thus suggested that the balance between t-PA and PAI-1 is important for the regulation of fibrinolysis. The release of t-PA and PAI-1 from vascular endothelial cells is regulated by physiological factors including thrombin (3,7), histamine (8), vasoconstrictor peptide endothelins (9,10) and cytokines (11). In addition, the regulation of the t-PA release and that of the PAI-1 release are not necessarily coupled. It has been shown that activated protein kinase C and cyclic AMP are involved in the stimulation and suppression, respectively, of the endothelial t-PA and PAI-1 production (12,13). However, the role of intracellular calcium in the regulation of endothelial t-PA and PAI-1 release has remained to be elucidated. In the present study, we investigated the effect of calcium ionophore A23187 on the release of t-PA antigen (t-PA:Ag) and PAI-1 antigen (PAI-1:Ag) from cultured vascular endothelial cells derived from human umbilical vein.
Department of Environmental Science, Faculty of Pharmaceutical Sciences, Hokuriku University, Japan.
C
C
Yamamoto
T
T
Kaji
M
M
Sakamoto
H
H
Kozuka
F
F
Koizumi
D000941:Antigens / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000276:immunology / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000276:immunology / Q000378:metabolism*
D000941:Antigens; D017395:Plasminogen Activator Inhibitor 1; D000001:Calcimycin; D010959:Tissue Plasminogen Activator; D002118:Calcium