Figure 2.

Functional assessment of carboxypeptidase U (CPU). The contribution of CPU to the total clot lysis time (ΔCLT; d) can be visualized by means of in vitro clot lysis experiments in the absence (a) or presence (b) of potato tuber carboxypeptidase inhibitor (PTCI) or a selective CPU inhibitor. During in vitro clot lysis, CPU is generated shortly after initiation of the coagulation—when proCPU is activated by thrombin(-thrombomodulin)—resulting in a first CPU activity peak (c) and halting fibrinolysis as long as the CPU level remains above a certain threshold value (e). This threshold concentration is dictated by steady-state plasmin concentrations, and thus dependent on tissue-type plasminogen activator (tPA) and plasmin inhibitor concentrations. Once CPU activity falls below this critical threshold value, fibrinolysis accelerates and the generated plasmin gives rise to the formation of a second CPU activity peak (c,e). The time that the CPU stays above the threshold (f) is defined by (1) the procarboxypeptidase U (proCPU) concentration, (2) the extent of proCPU activation—and thus the concentrations of thrombin(-thrombomodulin)—and (3) the CPU half-life, defined by the Thr/Ile325 polymorphism.