Inducible carboxypeptidase activity. A role in clot lysis in vivo.
BACKGROUND
An inducible carboxypeptidase activity in human plasma delays tissue-type plasminogen activator (TPA)-induced clot lysis in vitro. We investigated whether carboxypeptidase activity is induced in vivo during thrombosis and thrombolytic therapy in a canine model of myocardial infarction.


RESULTS
By use of synthetic substrate assays, dog plasma was shown to contain an inducible carboxypeptidase activity that is efficiently inhibited by potato carboxypeptidase inhibitor. This inhibitor accelerates TPA-mediated clot lysis in vitro by an average of 27% (n = 5, P = .046). Analysis of the inducible carboxypeptidase activity in plasma samples of dogs with electrically induced thrombosis of the circumflex coronary artery treated with TPA revealed that (1) inducible carboxypeptidase activity is increased during thrombosis (8.7 +/- 2.0 U/L, P < .013) and thrombolytic therapy (9.9 +/- 1.8 U/L, P < .024) compared with baseline (3.2 +/- 2.0 U/L); (2) thrombosis is a prerequisite of carboxypeptidase induction during and after TPA infusion, since carboxypeptidase levels were lower in dogs without a coronary thrombus; and (3) a significant positive correlation (r = .6, P < .0069) of carboxypeptidase activity with time to restoration of blood flow was observed.


CONCLUSIONS
These data indicate that carboxypeptidase activity is induced in vivo and may influence thrombolysis.
Redlitz
A
A
Joseph J.Jacobs Center for Thrombosis and Vascular Biology, The Cleveland Clinic Foundation, OH 44195, USA.
Nicolini
F A
FA
Malycky
J L
JL
Topol
E J
EJ
Plow
E F
EF
D000818:Animals; D025901:Carboxypeptidase B2; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D004285:Dogs; D004556:Electric Injuries; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology; D015425:Myocardial Reperfusion; D010940:Plant Proteins / Q000494:pharmacology; D011480:Protease Inhibitors; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000494:pharmacology / Q000627:therapeutic use
D010940:Plant Proteins; D011480:Protease Inhibitors; D002268:Carboxypeptidases; D025901:Carboxypeptidase B2; D010959:Tissue Plasminogen Activator