Abstract
Procarboxypeptidase U (proCPU, TAFI, proCPB2) is a basic carboxypeptidase zymogen that is converted by thrombin(-thrombomodulin) or plasmin into the active carboxypeptidase U (CPU, TAFIa, CPB2), a potent attenuator of fibrinolysis. As CPU forms a molecular link between coagulation and fibrinolysis, the development of CPU inhibitors as profibrinolytic agents constitutes an attractive new concept to improve endogenous fibrinolysis or to increase the efficacy of thrombolytic therapy in thromboembolic diseases. Furthermore, extensive research has been conducted on the in vivo role of CPU in (the acute phase of) thromboembolic disease, as well as on the hypothesis that high proCPU levels and the Thr/Ile325 polymorphism may cause a thrombotic predisposition. In this paper, an overview is given of the methods available for measuring proCPU, CPU, and inactivated CPU (CPUi), together with a summary of the clinical data generated so far, ranging from the current knowledge on proCPU concentrations and polymorphisms as potential thromboembolic risk factors to the positioning of different CPU forms (proCPU, CPU, and CPUi) as diagnostic markers for thromboembolic disease, and the potential benefit of pharmacological inhibition of the CPU pathway.
Highlights
The basic carboxypeptidase zymogen procarboxypeptidase U, known as thrombin-activatable fibrinolysis inhibitor (TAFI), procarboxypeptidase R or plasma procarboxypeptidase B, is predominantly synthesized by the liver and secreted into plasma [1,2,3,4,5]
CPU exerts its activity in a threshold-dependent manner: as long as the CPU level remains above a certain threshold value fibrinolysis is halted, but once the CPU activity drops below this level, plasmin formation is facilitated and the fibrinolysis will accelerate
There is a rationale that high proCPU levels carry a mild risk factor for the development of venous thrombosis
Summary
The basic carboxypeptidase zymogen procarboxypeptidase U (proCPU), known as thrombin-activatable fibrinolysis inhibitor (TAFI), procarboxypeptidase R (proCPR) or plasma procarboxypeptidase B (proCPB), is predominantly synthesized by the liver and secreted into plasma [1,2,3,4,5]. Upon activation by thrombin(-thrombomodulin) or plasmin, the key-enzymes of the coagulation and fibrinolysis respectively, the zymogen is converted into a potent attenuator of fibrinolysis: carboxypeptidase U (CPU, TAFIa, CPB2) [5,6,7]. CPU in (the acute phase of) thromboembolic disease, as well as on the hypothesis of that high proCPU levels or specific CPB2 gene variants may cause a thrombotic predisposition. Utmost importance to carefully by inherent advantageswell-characterized, and shortcomings,and so validated it is of utmost to carefully select an appropriate, assay importance when investigating the select an appropriate,role well-characterized, and (proCPU, validated CPU, assayand when investigating the (patho)physiological of specific CPU forms. Which can be measured with antigen-based that detect both CPU and CPUi simultaneously (5).
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