Declerck, P.J. (Paul J.)

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    Prevention of renal fibrin deposition in endotoxin-induced DIC through inhibition of PAI-1
    (Schattauer, 2000) Muñoz, M.C. (María Carmen); Rocha, E. (Eduardo); Hermida, J. (José); Montes, M. (Marta); Declerck, P.J. (Paul J.); Montes, R. (Ramón); Calvo-González, A. (Alfonso)
    Plasminogen activator inhibitor-1 (PAI-1) increases in endotoxemia thus possibly cooperating in altering the hemostatic balance in a prothrombotic direction. The effect of the inhibition of PAI-1 with the monoclonal antibody MA-33B8 was studied systemically and in kidneys in a lapine model of endotoxin-induced disseminated intravascular coagulation (DIC). The increase in plasmatic PAI activity in the control group (n = 9) was inhibited in the MA-33B8 treated rabbits (n = 5). Control rabbits showed renal fibrin deposits, whereas only one of the MA-33B8 rabbits did so. These results were confirmed immunohistochemically in kidneys as PAI-1 immunostaining was seen inside the glomeruli and larger vessels in the control group, whereas MA-33B8 rabbits showed a remarkable decrease, demonstrating that MA-33B8 successfully inhibited PAI-1 in the kidneys as well. Therefore evidence for the important role of PAI-1 in fibrin generation in endotoxin-induced DIC is presented, suggesting that strategies aiming at its reduction can be useful in this pathology.