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. METHODS AND 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.
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. METHODS AND 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.
Authors: Jason J Song; Inyong Hwang; Kyung H Cho; Michael A Garcia; Arthur J Kim; Tiffany H Wang; Tamsin M Lindstrom; Annette T Lee; Toshihiko Nishimura; Lei Zhao; John Morser; Michael Nesheim; Stuart B Goodman; David M Lee; S Louis Bridges; Peter K Gregersen; Lawrence L Leung; William H Robinson Journal: J Clin Invest Date: 2011-08-01 Impact factor: 14.808
Authors: Zuzana Valnickova; Laura Sanglas; Joan L Arolas; Steen V Petersen; Christine Schar; Daniel Otzen; Francesc X Aviles; F Xavier Gomis-Rüth; Jan J Enghild Journal: J Biol Chem Date: 2010-09-29 Impact factor: 5.157
Authors: Mirjam E Meltzer; Carine J M Doggen; Philip G de Groot; Joost C M Meijers; Frits R Rosendaal; Ton Lisman Journal: Haematologica Date: 2009-04-18 Impact factor: 9.941