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(Circulation Research. 2008;102:278.)
© 2008 American Heart Association, Inc.

Editorials

Glycosylation of Thrombin Activatable Fibrinolysis Inhibitor

Why Is it So Important?

Federico Biscetti

From the Laboratory of Vascular Biology and Genetics, Department of Medicine, A. Gemelli University Hospital, Catholic University School of Medicine, Rome, Italy.

Correspondence to Federico Biscetti, MD, Department of Medicine, A. Gemelli University Hospital, Catholic University School of Medicine, Rome, Italy. E-mail f.biscetti@gmail.com

See related article, pages 295–301

Key Words: TAFI • coagulation • fibrinolysis

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The coagulation and fibrinolytic systems safeguard the patency of the vasculature and the surrounding tissue. Regulation of these systems is accomplished by various mechanisms involving cellular responses, flow, and protein–protein interactions. Thrombin activatable fibrinolysis inhibitor (TAFI) is a fibrinolysis inhibitor, and its activation is sensitive to the dynamics of the coagulation system; it is one of the main intermediaries between coagulation and fibrinolysis. TAFI is a thrombin, thrombin/thrombomodulin and/or plasmin-activated enzyme that has greatly improved our understanding of the cross-regulation between coagulation and fibrinolysis, and its pathway modulates both the coagulation and the fibrinolytic system.^1,2

TAFI was identified at the same time by different groups, and this resulted in initial different names for the same protein^3–6: procarboxypeptidase U (pro-CPU), plasma procarboxypeptidase B (propCPB), and procarboxypeptidase R (pro-CPR). At the moment, TAFI is the most commonly used denomination.

TAFI is synthesized in the liver and secreted as a propeptide consisting of 401 amino acids.⁴ It has a molecular mass of 56 kDa. TAFI is activated by plasmin, by thrombin generated via the extrinsic or intrinsic coagulation pathways, or in presence of thrombomodulin.^7–10 Activated TAFI (TAFIa) inhibits fibrinolysis by modulating the fibrin cofactor function for plasmin generation. Proteolysis of C-terminal lysine residues of fibrin by TAFIa abrogates the fibrin cofactor function for tissue plasminogen activator–mediated plasminogen activation resulting in a plasmin formation suppression.¹¹

In recent years, there has been increasing appreciation of the fact that recombinant TAFI protein may have important therapeutic implications. In fact, antifibrinolytic therapy using TAFIa may help . . . [Full Text of this Article]

Related Article:

Biochemical Importance of Glycosylation in Thrombin Activatable Fibrinolysis Inhibitor

Karlien Buelens, Kerstin Hillmayer, Griet Compernolle, Paul J. Declerck, and Ann Gils
Circ. Res. 2008 102: 295-301. [Abstract] [Full Text] [PDF]