Synthesis and secretion of plasminogen activators and plasminogen activator inhibitor by endothelial cells

The vascular endothelium is generally thought to be the main source of t-PA in the blood, and to be involved in the regulation of the extrinsic fibrinolysis route. ¹ This view has been developed over a 30-year period, after Astrup and Permin ² demonstrated that human tissues contain an activator of plasminogen.* The first evidence that the endothelial cells are involved in fibrinolytic activity was given by Todd, ⁴ who developed a histological technique for the localization of fibrinolytic activity in tissue sections. Further evidence for the role of endothelial cells in fibrinolysis was obtained by immunolocalization studies, which demonstrated the presence of t-PA in endothelial cells of tissue slices, and by investigations on cultured endothelial cells. The latter studies have mainly been done on human and bovine endothelial cells. Endothelial cells in vitro not only produce t-PA, but also synthesize a potent PA inhibitor and are able to synthesize u-PA. The endothelial cell PA inhibitor is similar to the PA inhibitor in blood plasma and appears to be an important factor in the regulation of fibrinolysis. ⁵.