Українська Русский English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2015; 61(4): 78-84


ACTIVATION OF PROTEIN C IN THE IN VITRO THROMBOLYSIS

I.I. Patalakh, S.A.Talanov, O.V. Revka, T.F. Drobotko

    Palladin Institute of biochemistry National Academy of Sciences of Ukraine, Kyiv
DOI: https://doi.org/10.15407/fz61.04.078

Abstract

Physiological conditions of formation and subsequent lysis of thrombus were reconstituted in vitro in our research. Thrombus formation was initiated either by addition of exogenous thrombin or by contact of blood with anionic surface, which stimulates spontaneous coagulation of blood. Tissue plasminogen activator and/or protein C were previously added in the blood sample. The time of the beginning and total degradation of formed thrombi as well as the level of PC in lysates was controlled then. Only an addition of protein C alone or in combination with tissue plasminogen activator led to the most effective lysis of thrombi: their residual weight was 18% and 5% comparing to control. Addition of exogenous tissue plasminogen activator alone or in combination with protein C caused a 83% and 74% decrease of PC level in lysates of spontaneously formed thrombi, and 72% and 56% decrease for thrombi formed by thrombin, respectively. Without an addition of tissue plasminogen activator protein C level in lysates of thrombi formed by thrombin was 54% down on spontaneously formed thrombi. Thus, changes of PC concentration in isolated volume of clot seem to be controlled by thrombin at the stage of thrombus formation and by fibrinolytic system at the stage of fibrinolysis. Concentration of PC in lysates from clots formed by exogenous thrombin was decreasing over the next 10 hours of thrombolysis, which can also be the evidence of the interaction between the fibrinolytic and PC activation systems. A hypothesis is formulated about an existence of endothelium-independent mechanism of PC activation in blood plasma with blood cells participation, which effectiveness increases in the process of thrombolysis.

Keywords: protein C; activation; thrombin; tissue plasminogen activator; thrombus formation; thrombolysis; modeling.

References

  1. Di Cera E. Thrombin as procoagulant and anticoagulant.J Thromb Haemost 2007;5(Suppl. 1):196-202.
  2.  
  3. Rezaie A.R. Rapid Activation of Protein C by FactorXa and Thrombin in the Presence of PolyanionicCompounds. Blood. 1998;91(12):4572-80.
  4.  
  5. Varadi K., Philapitsch A., Santa T., Schwarz H.P. Activationand inactivation of human protein C by plasmin.Thromb Haemost 1994;71(5):615-21.
  6.  
  7. Hassouna H., Quinn C. Proteolysis of protein C in poolednormal plasma and purified protein C by activated proteinC (APC). Biophys Chem. 2002;95(2):109-24. CrossRef  
  8. McCachren S.S., Diggs J., Weinberg J.B., Dittman W.A.Thrombomodulin expression by human blood monocytesand by human synovial tissue lining macrophages. Blood.1991;78:3128-32.
  9.  
  10. Suzuki K., Nishioka J., Hayashi T., Kosaka Y. Functionallyactive thrombomodulin is present in human platelets. JBiochem. 1988;104:628-63.
  11.  
  12. Takahashi H., Hanano M., Tatewaki W., Shibata A. Fastfunctional assay of protein C in whole plasma usinga snake venom activator: evaluation in patients withcongenital and acquired protein C deficiencies. ClinChim Acta. 1988;175(3):217-25. CrossRef  
  13. Anand M., Rajagopal K., Rajagopal K.R. A model forthe formation, growth, and lysis of clots in quiescentplasma. A comparison between the effects of antithrombinIII deficiency and protein C deficienc. J Theor Biol.2008;253:725-38. CrossRef PubMed
  14.  
  15. Gruber A., Mori E., del Zoppo G.J., Waxman L., GriffinJ.H. Alteration of fibrin network by activated protein C.Blood. 1994;83(9):2541-48.
  16.  
  17. Wohner N. Role of cellular elements in thrombus formationand dissolution. Cardiovasc Hematol Agents MedChem. 2008;6(3):224–28. CrossRef  
  18. Heeb M.J., Gruber A, Griffin J.H. Identification ofdivalent metal ion-dependent inhibition of activatedprotein C by alpha 2-macroglobulin and alpha2-antiplasmin in blood and comparisons to inhibitionof factor Xa, thrombin, and plasmin. J Bio. Chem.1991;266(26):17606-12.
  19.  
  20. Varin R., Mirshahi S. , Mirshahi P., Klein C., JamshedovJ., Chidiac J., Perzborn E., Mirshahi M., Soria C., SoriaJ. Whole blood clots are more resistant to lysis thanplasma clots - greater efficacy of rivaroxaban. ThrombRes. 2013;131:e100-e109.
  21.  
  22. Hemker H. C., Giesen P. L. A., Ramjee M., WagenvoordR., Beguin S. The Thrombogram: Monitoring ThrombinGeneration in Platelet Rich Plasma. Thromb Haemost.2000;83:589-91.
  23.  

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2019.