Plasma carboxypeptidase U (CPU, CPB2, TAFIa) generation during in vitro clot lysis and its interplay between coagulation and fibrinolysis
| Autor: | Yani Sim, Jef Aernouts, Dirk Hendriks, Dorien Leenaerts, Anne-Marie Lambeir, Pieter Van der Veken |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Male Carboxypeptidase B2 Time Factors Carboxypeptidase U Genotype Plasmin medicine.medical_treatment Thrombomodulin 030204 cardiovascular system & hematology 03 medical and health sciences Young Adult 0302 clinical medicine Thrombin Fibrinolysis medicine Humans Fibrinolysin Blood Coagulation Aged Aged 80 and over Polymorphism Genetic biology Chemistry Hematology Middle Aged Carboxypeptidase In vitro Healthy Volunteers Enzyme Activation 030104 developmental biology Clot lysis Phenotype Biochemistry biology.protein Biophysics Female Blood Coagulation Tests Human medicine Algorithms Biomarkers medicine.drug |
| Zdroj: | Thrombosis and haemostasis : international journal for vascular biology and medicine |
| ISSN: | 0340-6245 |
| Popis: | SummaryCarboxypeptidase U (CPU, CPB2, TAFIa) is a basic carboxypeptidase that is able to attenuate fibrinolysis. The inactive precursor procarboxypeptidase U is converted to its active form by thrombin, the thrombin-thrombomodulin complex or plasmin. The aim of this study was to investigate and characterise the time course of CPU generation in healthy individuals. In plasma of 29 healthy volunteers, CPU generation was monitored during in vitro clot lysis. CPU activity was measured by means of an enzymatic assay that uses the specific substrate Bz-o-cyano-Phe-Arg. An algorithm was written to plot the CPU generation curve and calculate the parameters that define it. In all individuals, CPU generation was biphasic. Marked inter-individual differences were present and a reference range was determined. The endogenous CPU generation potential is the composite effect of multiple factors. With respect to the first CPU activity peak characteristics, we found correlations with baseline proCPU concentration, proCPU Thr325Ile polymorphism, time to clot initiation and the clot lysis time. The second CPU peak related with baseline proCPU levels and with the maximum turbidity of the clot lysis profile. In conclusion, our method offers a technique to determine the endogenous CPU generation potential of an individual. The parameters obtained by the method quantitatively describe the different mechanisms that influence CPU generation during the complex interplay between coagulation and fibrinolysis, which are in line with the threshold hypothesis.Supplementary Material to this article is available online at www.thrombosis-online.com. |
| Databáze: | OpenAIRE |
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