Plasminogen and Plasminogen Activator Assembly on the Human Endothelial Cell

Abstract

Summary

Through assembly of plasminogen and its activators, the endothelial cell surface may provide a favorable environment for constitutive generation of plasmin. This system may be regulated at multiple levels. Abundant expression of a 40-kDa protein with dual ligand-binding capacity may promote cell surface plasmin formation by colocalizing t-PA and plasminogen in a catalytically favorable configuration. Conversion of Glu-PLG to the preactivated form Lys-PLG, in the vicinity of the cell surface, may also precede plasmin formation. Physiologic concentrations of Lp(a), furthermore, may serve to modulate plasminogen activation at the cell surface by competing for binding sites, whereas elevated levels of Lp(a) might suppress this mechanism and lead to a subclinical prothrombotic state. Finally, cell surface binding sites for both plasmin and t-PA appear to protect these molecules from their physiologic antagonists, α₂-plasmin inhibitor and plasminogen activator inhibitor, type-1, respectively. Plasmin formation may contribute to the nonthrombogenicity of the blood vessel wall.

This work was supported by the NIH (HL 42493, HL 46403, HL 18828), the American Heart Association, with funds contributed by the New York affiliate, and the Council for Tobacco Research-USA, Inc. Dr. Hajjar is a Syntex Scholar and an Established Investigator of the American Heart Association.