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
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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.
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