Carboxypeptidase U (CPU) is a basic metallocarboxypeptidase discovered in the Laboratory of Medical Biochemistry, and is currently considered as an important link between the coagulation system and fibrinolysis.
The maintenance of the equilibrium between coagulation and fibrinolysis is crucial for normal haemostasis. When both systems are not properly balanced the pathological consequences are reflected in a tendency to bleed or develop thrombosis.
Carboxypeptidase U (CPU) functions at the interfase between coagulation and fibrinolysis. On activation by thrombin, CPU exerts and antifibrinolytic effect by removing C-terminal lysine residues on partially degraded fibrin, thus abolishing the cofactor function of this partially degraded fibrin in plasminogen activation.
We study the role of the proCPU/CPU pathway in the balance between fibrin deposition and removal, and how a disturbed system can lead to a thrombotic tendency. Moreover we focus on evaluating CPU inhibition as a new drug target for fibrinolytic therapy in conditions such as deep vein thrombosis, pulmonary embolism, myocardial infarction and thrombotic stroke.
Literature
- Heylen E, Van Goethem S, Augustyns K, Hendriks D. Measurement of carboxypeptidase U (active thrombin-activatable fibrinolysis inhibitor) in plasma: Challenges overcome by a novel selective assay. Anal Biochem. 2010;403(1-2):114-6.
- Brouns R, Heylen E, Willemse JL, Sheorajpanday R, De Surgeloose D, Verkerk R, De Deyn PP, Hendriks DF. The decrease in procarboxypeptidase U (TAFI) concentration in acute ischemic stroke correlates with stroke severity, evolution and outcome. J Thromb Haemost. 2010;8(1):75-80.
- Hendriks Dirk, Heylen Evelien,Willemse Johan. An update on the role of carboxypeptidase U (TAFIa) in fibrinolysis. Frontiers in bioscience : landmark-issn 1093-9946-16(2011),p. 2427-2450
- Leurs J, Nerme V, Sim Y, Hendriks D. Carboxypeptidase U (TAFIa) prevents lysis from proceeding into the propagation phase through a threshold-dependent mechanism. J Thromb Haemost. 2004;2(3):416-23