Regulation of factor VIIa/tissue factor functional activity in an umbilical vein model.
Activation of factor IX in an umbilical vein model was established to result solely from factor VIIa/tissue factor (TF) activity generated within the umbilical vein wall, and the model was then used to study regulation of such extravascular factor VIIa-TF complexes. Vein segments were filled with a reaction mixture containing factor VIIa, Ca2+, a substrate, either [3H]factor IX or [3H]factor X, and a test material. Subsamples were assayed for activation peptide release. Test materials included defibrinated plasma or recombinant protein as a source of TF pathway inhibitor (TFPI), recombinant factor VIIa to 10 times plasma factor VII concentrations, and annexin V. A plasma concentration of TFPI inhibited but did not totally suppress factor VIIa/TF activity. Reducing the TFPI concentration by 50% markedly reduced the inhibition. A 10-fold increase in the factor VIIa concentration in reaction mixtures failed to accelerate factor Xa generation. Annexin V, in contrast to its inhibition of factor VIIa/TF formed with TF reconstituted into mixed phospholipid vesicles, failed to inhibit factor VIIa-TF complexes formed within the vessel wall. We conclude that 1) moderate variation in plasma TFPI concentration or activity may affect TFPI's ability to inhibit factor VIIa/TF activity during hemostasis, 2) a plasma concentration of factor VII suffices to saturate TF sites exposed in a vessel after tissue injury, and 3) the resistance of factor VIIa-TF complexes to inhibition by annexin V suggests that they are formed in the umbilical vein model primarily on cell surfaces.
Almus
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Department of Medicine, University of California, San Diego, School of Medicine, La Jolla.
Rao
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Rapaport
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D000838:Anions / Q000378:metabolism; D017304:Annexin A5 / Q000494:pharmacology; D015942:Factor VIIa / Q000502:physiology*; D015951:Factor Xa / Q000032:analysis; D006801:Humans; D066298:In Vitro Techniques; D009994:Osmolar Concentration; D010743:Phospholipids / Q000378:metabolism; D011994:Recombinant Proteins; D013917:Thrombin / Q000096:biosynthesis; D013925:Thromboplastin / Q000037:antagonists & inhibitors / Q000502:physiology*; D014471:Umbilical Veins / Q000378:metabolism / Q000502:physiology*
D000838:Anions; D017304:Annexin A5; D010743:Phospholipids; D011994:Recombinant Proteins; D013925:Thromboplastin; D015942:Factor VIIa; D013917:Thrombin; D015951:Factor Xa