Abstract
To delineate the role of binding of urokinase type plasminogen activator (uPA) to its receptor (uPAR) in the local generation of plasmin by endothelium, we transfected spontaneously transformed immortalized human vascular endothelial cells that express high levels of uPA but low levels of uPAR with human uPAR complementary DNA. Compared with nontransfected cell, the stably transformed clonal cell line exhibited (a) a > 10-fold increase in steady-state uPAR mRNA levels documented with Northern blot analysis (n = 3), (b) a 2.8-fold increase in cell surface expression of uPAR protein quantified by enzyme linked immunosorbent assay (n = 3), (c) a 2.9-fold increase in specific binding of radiolabeled single chain uPA (n = 4), and (d) markedly increased matrix adhesion. The participation of uPAR in cell surface proteolysis was apparent based on a 3.0-fold increase in cell associated plasmin activity (n = 3) and a 2.3-fold increase in lysis of noncrosslinked fibrin clots (n = 5). Thus, local generation of plasmin and consequent degradation of fibrin are likely to be promoted by cell surface localization of uPA by uPAR in cellular constituents of the vessel wall. Furthermore, genetic engineering of endothelium to enhance expression of uPAR may confer resistance to thrombosis or restenosis associated with endovascular stents.
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Sawa, H., Lundgren, C.H., Brown, S.L. et al. Dependence of human vascular cell surface proteolysis on expression of the urokinase receptor. J Thromb Thrombol 3, 331–336 (1996). https://doi.org/10.1007/BF00133076
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DOI: https://doi.org/10.1007/BF00133076