CPB2

CPB2 Full Name

carboxypeptidase B2 (plasma)

CPB2 Introduction

CPB2, also called carboxypeptidase B2 or thrombin-activatable fibrinolysis inhibitor (TAFI), is a proenzyme synthesized in the liver and present in plasma. It is activated by the thrombin–thrombomodulin complex during coagulation. Activated CPB2 also trims C-terminal lysine residues from fibrin. Degradation of lysine residues in fibrin abrogates plasminogen binding to fibrin, resulting in a decrease in fibrinolytic rate. Confirmation of CPB2's biochemical properties, regulation and activation pathway in animal models and in patients further substantiates the present view of its role in the coagulation/fibrinolysis equilibrium.

Figure 1. Inactivation of complement anaphylatoxins by carboxypeptidase B2 (CPB2) and carboxypeptidase N (CPN).(Source: Leung LLK, et al.; 2018)

Biologically, CPB2 plays an essential role as an endogenous antifibrinolytic. It has a role in stabilizing clot architecture and in controlling the length of time that fibrin remains at the site of vessel damage. This is achieved through limiting the production of plasmin. If CPB2 is delayed or deficient, there is increased fibrinolysis. This could be beneficial in reducing the risk of thrombosis, but can also lead to a propensity to bleed. CPB2 is also regulated by inflammatory signals as CPB2 is capable of cleaving the inflammatory peptides C3a and C5a. This also indicates that CPB2 has roles in coagulation–inflammation interactions.

Alterations in the expression or activity of CPB2 have been implicated in a number of diseases. An increase in CPB2 activity has been observed in thrombosis, stroke, venous thromboembolism, and cardiovascular disease. In these conditions, pathological clot stability is, at least in part, maintained by an increase in antifibrinolytic activity. In contrast, bleeding can occur when CPB2 is low or is present as a genetic variant that is rapidly inactivated by protein-protease complexes. A decrease in CPB2 expression or activity has also been implicated in sepsis, liver disease, and metabolic disease. In these conditions, dysregulated coagulation–inflammation crosstalk is thought to contribute to pathogenesis. CPB2's plasma activity can be easily measured and it has a well-characterised mechanistic role in disease making it a clinically relevant biomarker and drug target in disease states that involve aberrant fibrinolysis.

Alternate Names for CPB2

CPB2; carboxypeptidase B2 (plasma); CPU; PCPB; TAFI; carboxypeptidase B2; carboxypeptidase R; carboxypeptidase B-like protein; thrombin-activable fibrinolysis inhibitor; thrombin-activatable fibrinolysis inhibitor; carboxypeptidase B2 (plasma, carboxypeptidase U);

• 1. Leung LLK, Morser J. Carboxypeptidase B2 and carboxypeptidase N in the crosstalk between coagulation, thrombosis, inflammation, and innate immunity. J Thromb Haemost. 2018 Jun 8. PMID: 29883024.