Plasminogen II accumulates five times faster than plasminogen I at the site of a balloon de-endothelializing injury in vivo to the rabbit aorta: comparison with other hemostatic proteins.
In the rabbit blood stream, plasminogen circulates as two glycoforms, plasminogen I (PLG-I) and plasminogen II (PLG-II), in a molar ratio of 1:2.2. To compare their relative behaviors toward a site of vascular injury, radiolabeled samples of PLG-I and PLG-II were coinjected intravenously into NZW rabbits before inducing a de-endothelializing (balloon catheter) injury to the thoracic aorta. At various times (5 to 60 minutes) after injury, each rabbit was anesthetized and exsanguinated, the aorta was excised, and the radioactivity per centimeters squared of aortic intima-media (IM) was measured relative to that of blood at exsanguination. The uptake of iodine 125-labeled PLG-I and iodine 131-labeled PLG-II showed that the IM was essentially saturated by both glycoforms by 30 to 40 minutes after injury. Extrapolation of the flux rates to 1 minute after injury indicated that the uptake of PLG-II (2.4 pmol/min/cm2) exceeded PLG-I (0.5 pmol/min/cm2) almost five-fold. This result is consistent with an earlier report (Metabolism 1994;43:1430-7) that PLG-II is released by the liver and catabolized in vivo approximately five times faster than PLG-I. By molar comparison, the flux of total plasminogen (ie, PLG-I plus PLG-II) into the injured aorta wall in vivo was 2.4 times greater than that for prothrombin. Assuming both zymogens are converted to their respective proteases within the wound site, then approximately 2 to 3 molecules of plasmin are released for each molecule of thrombin in vivo. The possible significance of this plasmin:thrombin ratio is discussed in respect to the turnover of fibrin(ogen) within the site of vascular injury.
Hatton
M W
MW
Department of Pathology and Molecular Medicine, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.
Day
S
S
Ross
B
B
Southward
S M
SM
DeReske
M
M
Richardson
M
M
D000818:Animals; D000991:Antithrombins / Q000378:metabolism; D001013:Aorta, Thoracic / Q000293:injuries* / Q000378:metabolism*; D002404:Catheterization / Q000009:adverse effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000293:injuries* / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D006031:Glycosylation; D006487:Hemostasis; D015844:Heparin Cofactor II / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010958:Plasminogen / Q000302:isolation & purification / Q000378:metabolism*; D020033:Protein Isoforms / Q000302:isolation & purification / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D011817:Rabbits
D000991:Antithrombins; D020033:Protein Isoforms; D015844:Heparin Cofactor II; D011516:Prothrombin; D005340:Fibrinogen; D010958:Plasminogen