REGULATION OF ENDOTHELIAL-CELL PROTEIN-C ACTIVATION AND FIBRINOLYSIS BY PROCOAGULANT ALBUMIN

Endothelial cell regulation of protein C activation and fibrinolysis a re important components of the hemostatic response to vascular injury or perturbation. Procoagulant albumin (P-Al), a constituent of normal human plasma has been purified and identified as an inducer of endothe lial cell tissue factor activity. The purpose of the studies reported herein was to investigate the effects of P-Al on human endothelial cel l protein C activation and fibrinolysis. P-Al suppressed protein C act ivation, enhanced release of plasminogen activator inhibitor-1, but ha d no effect on tissue-plasminogen activator release. Plasminogen activ ator inhibitor-1 released by P-Al was functional as evidenced by the c apacity to form a covalent complex with I-125-urokinase. Inactive albu min (isolated during the same purification procedure as P-Al, but with out tissue factor-inducing activity) did not suppress protein C activa tion or increase plasminogen activator inhibitor-1 release. There resu lts indicate that P-Al, a component of human plasma, can modulate mult iple vascular hemostatic properties, and support the hypothesis that P -Al is involved in normal or pathologic hemostasis.