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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:2245-2250.)
© 1999 American Heart Association, Inc.

Thrombosis

Kininogens Are Antithrombotic Proteins In Vivo

Robert W. Colman; John V. White; Sherry Scovell; Antoni Stadnicki; R. Balfour Sartor

From the Sol Sherry Thrombosis Research Center (R.W.C., A.S.) and the Department of Surgery (J.V.W., S.S.), Temple University School of Medicine, Philadelphia, Pa, and the Division of Digestive Diseases and Sciences (R.B.S.), University of North Carolina, Chapel Hill.

Correspondence to Robert W. Colman, MD, Sol Sherry Thrombosis Research Center, Temple University School of Medicine, 3400 N Broad St, Philadelphia, PA 19140. E-mail colmanr{at}astro.temple.edu

Abstract—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 properties in vivo, we devised a model of limited arterial injury confined to removal of the endothelium. Brown-Norway Katholiek strain rats with an absence of low- and high-molecular-weight kininogen due to a single point mutation, 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 laser Doppler was 38.4±17 minutes in the kininogen-deficient rats compared with 194±29 minutes in the wild-type animals (P<0.002). The degree of vascular injury was the same. No evidence for disseminated intravascular coagulation (decrease in factor V, antithrombin, or fibrinogen) or excessive fibrinolysis (elevation of fibrinogen degradation products) was found in either group of animals. The results suggest that kininogens have antithrombotic properties at low concentrations of thrombin and that inhibitory peptides derived from kininogen may constitute a new antithrombotic strategy.

Key Words: arterial thrombosis • kininogens • antithrombotic • fibrinolysis • rats

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