An Increased Uptake of Prothrombin, Antithrombin, and Fibrinogen by the Rabbit Balloon-Deendothelialized Aorta Surface In Vivo Is Maintained Until Reendothelialization Is Complete

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Abstract
The ability of the rabbit aorta intima-media (IM) layer to adsorb certain plasma proteins was measured for up to 20 months after a deendothelializing injury in vivo. Purified radioiodinated rabbit fibrinogen, antithrombin, or prothrombin was injected intravenously into either uninjured or sham-injured rabbits (controls) or rabbits at various times (5 minutes to 20 months) after a balloon-catheter injury to the aorta. After a 10-minute circulation time, a blood sample was taken, and the rabbit was exsanguinated rapidly (via a carotid cannula) and the aorta excised. Uptake of each radiolabeled protein was measured as bound radioactivity per square centimeter of platelet- or endothelium-free aorta IM and was compared with the radioactivity (ergo concentration) in blood at exsanguination. Fibrinogen adsorption by the IM was maximal at 5 minutes after injury (10.9±2.3 pmol/cm 2 IM) and declined slowly to 4 to 6 pmol/cm 2 at 12 months (controls: 0.8±0.1 pmol/cm 2 ). Uptake of prothrombin (3.7±0.5 pmol/cm 2 at 5 minutes) decreased to ≈2 pmol/cm 2 at 12 months (controls: 0.3 pmol/cm 2 ). Antithrombin adsorption by the IM (3.3±0.4 pmol/cm 2 at 5 minutes) paralleled that of prothrombin over 12 months (controls: 0.3 to 0.4 pmol/cm 2 ), the molar ratio ranging from 0.8 to 1.2. At 20 months, the ballooned aorta had a significantly thickened intima and was ≈90% reendothelialized. Injection of horseradish peroxidase (HRP) into rabbits at 1 or 12 months after balloon injury showed clearly that HRP activity was present throughout the entire depth of the deendothelialized, but not the reendothelialized, thickened intima. These results may indicate that an elevated turnover of hemostatic proteins continues within the deendothelialized intima after injury, conceivably until reendothelialization is complete.