Ambivalent roles of carboxypeptidase B in the lytic susceptibility of fibrin.

Content Provider	Europe PMC
Author	Kovács, András Szabó, László Longstaff, Colin Tenekedjiev, Kiril Machovich, Raymund Kolev, Krasimir
Copyright Year	2013
Abstract	BackgroundRemoval of C-terminal lysine residues that are continuously exposed in lysing fibrin is an established anti-fibrinolytic mechanism dependent on the plasma carboxypeptidase TAFIa, which also removes arginines that are exposed at the time of fibrinogen clotting by thrombin.ObjectiveTo evaluate the impact of alterations in fibrin structure mediated by constitutive carboxypeptidase activity on the function of fibrin as a template for tissue plasminogen activator-(tPA) induced plasminogen activation and its susceptibility to digestion by plasmin.Methods and resultsWe used the stable carboxypeptidase B (CPB), which shows the same substrate specificity as TAFIa. If 1.5 – 6 μM fibrinogen was clotted in the presence of 8 U/mL CPB, a denser fibrin network was formed with thinner fibers (the median fiber diameter decreased from 138 – 144 nm to 89 – 109 nm as established with scanning electron microscopy). If clotting was initiated in the presence of 5 – 10 μM arginine, a similar decrease in fiber diameter (82 -95 nm) was measured. The fine structure of arginine-treated fibrin enhanced plasminogen activation by tPA, but slowed down lysis monitored using fluorescent tPA and confocal laser microscopy. However, if lysis was initiated with plasmin in CPB-treated fibrin, the rate of dissolution increased to a degree corresponding to doubling of the plasmin concentration.ConclusionThe present data evidence that CPB activity generates fine-mesh fibrin which is more difficult to lyse by tPA, but conversely, CPB and plasmin together can stimulate fibrinolysis, possibly by enhancing plasmin diffusion.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC3891004&blobtype=pdf
ISSN	00493848
Journal	Thrombosis Research [Thromb Res]
Volume Number	133
DOI	10.1016/j.thromres.2013.09.017
PubMed Central reference number	PMC3891004
Issue Number	1
PubMed reference number	24094605
e-ISSN	18792472
Language	English
Publisher	Pergamon Press
Publisher Date	2013-09-21
Access Restriction	Open
Rights License	This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/3.0/). © 2013 The Authors
Subject Keyword	CPB, carboxypeptidase B CPN, carboxypeptidase N TAFI, thrombin activatable fibrinolysis inhibitor tPA, tissue-type plasminogen activator Carboxypeptidase Fibrin Fibrinolysis Plasmin tPA
Content Type	Text
Resource Type	Article
Subject	Hematology