Regulation of endothelial cell protein C activation and fibrinolysis by procoagulant albumin.
Endothelial cell regulation of protein C activation and fibrinolysis are important components of the hemostatic response to vascular injury or perturbation. Procoagulant albumin (P-A1), a constituent of normal human plasma has been purified and identified as an inducer of endothelial cell tissue factor activity. The purpose of the studies reported herein was to investigate the effects of P-A1 on human endothelial cell protein C activation and fibrinolysis. P-A1 suppressed protein C activation, enhanced release of plasminogen activator inhibitor-1, but had no effect on tissue-plasminogen activator release. Plasminogen activator inhibitor-1 released by P-A1 was functional as evidenced by the capacity to form a covalent complex with 125I-urokinase. Inactive albumin (isolated during the same purification procedure as P-A1, but without tissue factor-inducing activity) did not suppress protein C activation or increase plasminogen activator inhibitor-1 release. These results indicate that P-A1, a component of human plasma, can modulate multiple vascular hemostatic properties, and support the hypothesis that P-A1 is involved in normal or pathologic hemostasis.
Gubler
D B
DB
Department of Medicine, University of Utah Medical Center, Salt Lake City.
Wilson
B D
BD
Parker
C J
CJ
Rodgers
G M
GM
D000838:Anions; D001779:Blood Coagulation Factors / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005342:Fibrinolysis / Q000502:physiology*; D006487:Hemostasis / Q000502:physiology; D006801:Humans; D011486:Protein C / Q000378:metabolism*; D012709:Serum Albumin / Q000502:physiology*; D013925:Thromboplastin / Q000096:biosynthesis
D000838:Anions; D001779:Blood Coagulation Factors; D011486:Protein C; D012709:Serum Albumin; D013925:Thromboplastin