Modulation by Endothelin-1 of Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 Release from Cultured Human Vascular Endothelial Cells : Interaction of Endothelin-1 with Cytokines

Abstract

The interaction of endothelin-1 (ET-1) with either interleukin-1 β (IL-1 β) or tumor necrosis factor α (TNF α) on the release of tissue plasminogen activator antigen (t-PA : Ag) and plasminogen activator inhibitor-1 antigen (PAI-1 : Ag) was investigated in a culture system of vascular endothelial cells derived from human umbilical vein. The t-PA : Ag release was significantly decreased by either IL-1 β or TNF α; ET-1 intensified the suppressive effect of the cytokines. In contrast, PAI-1 : Ag release was significantly increased by either IL-1 β or TNF α; ET-1 significantly reduced the stimulatory effect of the cytokines. The data suggest that endothelial cell-mediated fibrinolysis may be modulated by ET-1.