Regulation of the synthesis and secretion of plasminogen activators by endothelial cells

Plasminogen activators (PAs) play a role in fibrinolysis, tissue remodelling, tumor invasion, and reparative processes. Vascular endothelial cells produce tissue-type PA (t-PA), an important regulator of fibrinolysis, and PA inhibitor 1. They can also synthesize a second type of PA, urokinase-type PA (u-PA). The regulation of synthesis and secretion of these PAs by human and bovine endothelial cells in vitro is reviewed. The synthesis of t-PA and u-PA varies between endothelial cells, depending on their vascular origin. The production of PA activity by endothelial cells is regulated at various levels: (1) induction of newly synthesized t-PA or u-PA molecules; (2) rapid release of t-PA from endothelial cells; (3) conversion of single-chain u-PA in the more active two-chain u-PA; (4) interaction of PAs with cellular receptors and matrix components, and (5) interaction of PAs with specific inhibitors.