Kininogens are antithrombotic proteins in vivo

Kininogens have recently been shown to possess antiadhesive, anticoagulant, and profibrinolytic properties and can inhibit platelet activation at low thrombin concentrations. To test whether kininogens have antithrombotic pro perties in vivo, we devised a model of limited arterial injury confined to removal of the endothelium. Brown-Norway Katholiek strain rats with an abse nce of low- and high-molecular-weight kininogen due to a single point mutat ion, A163T, were compared in the thrombosis model to the wild-type animals, which were otherwise genetically identical. Despite an equivalent vascular injury, the mean time (+/-SEM) for a 90% decrease in flow measured by lase r Doppler was 38.4+/-17 minutes in the kininogen-deficient rats compared wi th 194+/-29 minutes in the wild-type animals (P<0.002), The degree of vascu lar injury was the same. No evidence for disseminated intravascular coagula tion (decrease in factor V, antithrombin, or fibrinogen) or excessive fibri nolysis (elevation of fibrinogen degradation products) was found in either group of animals. The results suggest that kininogens have antithrombotic p roperties at low concentrations of thrombin and that inhibitory peptides de rived from kininogen may constitute a new antithrombotic strategy.