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Ambivalent roles of carboxypeptidase B in the lytic susceptibility of fibrin


Kovacs, A and Szabo, L and Longstaff, C and Tenekedjiev, K and Machovich, R and Kolev, K, Ambivalent roles of carboxypeptidase B in the lytic susceptibility of fibrin, Thrombosis Research, 133, (1) pp. 80-87. ISSN 0049-3848 (2014) [Refereed Article]


Copyright Statement

Copyright 2013 The Authors. Licensed under Creative Commons Attribution 3.0 Unported (CC BY 3.0)

DOI: doi:10.1016/j.thromres.2013.09.017


Background: Removal 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.

Objective: To 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 results: We 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.

Conclusion: The 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.

Item Details

Item Type:Refereed Article
Keywords:lytic susceptibility, fibrin, mathematical modelling, carboxypeptidase, fibrin, fibrinolysis, plasmin, tPA
Research Division:Mathematical Sciences
Research Group:Statistics
Research Field:Applied statistics
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the information and computing sciences
UTAS Author:Tenekedjiev, K (Professor Kiril Tenekedjiev)
ID Code:116179
Year Published:2014
Web of Science® Times Cited:14
Deposited By:NC Maritime Engineering and Hydrodynamics
Deposited On:2017-05-03
Last Modified:2017-11-03
Downloads:145 View Download Statistics

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