Uptake of heparin cofactor II and antithrombin into the aorta wall after adeendothelializing injury in vivo: Comparison with the behaviors of prothrombin and fibrinogen

The initiation of a denuding injury to the vascular endothelium rapidly lea ds to a deposition of platelets and fibrin at the site of injury. We have m easured previously the responses of rabbit fibrinogen, prothrombin, and ant ithrombin to a deendothelializing balloon-catheter injury to the rabbit aor ta in vivo. In this study, rabbit iodine 125-labeled HCII and iodine 125-la beled AT were coinjected intravenously into anesthetized rabbits 5 minutes before deendothelialization of the thoracic aorta. The rabbit was exsanguin ated at 5 to 60 minutes after injury, the aorta was excised, and the accumu lation of each radiolabeled protein in each layer of aorta wall was determi ned relative to the concentration of the respective native protein in circu lating blood at exsanguination. The maximum flux rates into the aorta wall (ie, platelet layer and intima-media) in the first minute after injury were calculated from the uptake data; approximately 2.8 molecules of AT accumul ated for each HCII molecule. By comparison with previous measurements, the maximum flux rate of AT was similar to that of prothrombin. further, the mo lar ratio of accumulated prothrombin/AT + HCII) in the aorta wall was 0.75. Detergent extracts of the injured aorta intima-media contained unreacted H CII and HCII complexes; the uninjured aorta contained only unreacted HCII. By contrast, high molecular weight AT complexes and unreacted AT were extra cted from the uninjured, and in greater quantity from the injured, aorta wa ll. We conclude that, of the plasma antithrombins, AT accumulated more rapi dly than HCII in vivo and appeared to be the more active inhibitor at the s ite of vascular injury. HCII may play a relatively minor role as an antithr ombin and possibly only after injury.