Uptake of heparin cofactor II and antithrombin into the aorta wall after a deendothelializing injury in vivo: comparison with the behaviors of prothrombin and fibrinogen.
The initiation of a denuding injury to the vascular endothelium rapidly leads to a deposition of platelets and fibrin at the site of injury. We have measured previously the responses of rabbit fibrinogen, prothrombin, and antithrombin to a deendothelializing balloon-catheter injury to the rabbit aorta in vivo. In this study, rabbit iodine 125-labeled HCII and iodine 125-labeled AT were coinjected intravenously into anesthetized rabbits 5 minutes before deendothelialization of the thoracic aorta. The rabbit was exsanguinated at 5 to 60 minutes after injury, the aorta was excised, and the accumulation of each radiolabeled protein in each layer of aorta wall was determined relative to the concentration of the respective native protein in circulating blood at exsanguination. The maximum flux rates into the aorta wall (i.e., platelet layer and intima-media) in the first minute after injury were calculated from the uptake data; approximately 2.8 molecules of AT accumulated for each HCII molecule. By comparison with previous measurements, the maximum flux rate of AT was similar to that of prothrombin. Further, the molar ratio of accumulated prothrombin/AT + HCII) in the aorta wall was 0.75. Detergent extracts of the injured aorta intima-media contained unreacted HCII and HCII complexes; the uninjured aorta contained only unreacted HCII. By contrast, high molecular weight AT complexes and unreacted AT were extracted from the uninjured, and in greater quantity from the injured, aorta wall. We conclude that, of the plasma antithrombins, AT accumulated more rapidly than HCII in vivo and appeared to be the more active inhibitor at the site of vascular injury. HCII may play a relatively minor role as an antithrombin and possibly only after injury.
Hatton
M W
MW
Department of Pathology (HSC-4N67), McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.
Ross
B
B
Southward
S M
SM
Dereske
M
M
Hoogendoorn
H
H
Blajchman
M A
MA
Richardson
M
M
D000818:Animals; D000991:Antithrombins / Q000378:metabolism*; D001013:Aorta, Thoracic / Q000293:injuries / Q000378:metabolism*; D002404:Catheterization / Q000379:methods; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000293:injuries / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D015844:Heparin Cofactor II / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008297:Male; D011516:Prothrombin / Q000378:metabolism*; D011817:Rabbits
D000991:Antithrombins; D007457:Iodine Radioisotopes; D015844:Heparin Cofactor II; D011516:Prothrombin; D005340:Fibrinogen