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Blood, 15 July 2002, Vol. 100, No. 2, pp. 539-546
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Activated protein C cleaves factor Va more efficiently on
endothelium than on platelet surfaces
Julie A. Oliver,
Dougald M. Monroe,
Frank C. Church,
Harold R. Roberts, and
Maureane Hoffman
From Duke University and the Durham VA Medical
Hospital, Durham, NC; and the University of North Carolina, Chapel
Hill.
The protein C/protein S system is known to regulate thrombin
generation in vivo by cleaving factors Va and VIIIa. We have examined
the activity of activated protein C in several tissue factor-initiated
models of coagulation. We used 4 models: monocytes as the tissue factor
source with platelets as the thrombin-generating surface; endothelial
cells as the tissue factor source with platelets as the
thrombin-generating surface; endothelial cells as both the tissue
factor source and the thrombin-generating surface; and relipidated
tissue factor with lipid vesicles providing the surface for thrombin
generation. With the lipid surface, activated protein C
dose-dependently reduced thrombin generation. Similarly, when
endothelial cells provided the only surface for thrombin generation,
activated protein C dose-dependently decreased thrombin generation
significantly. By contrast, whenever platelets were present, activated
protein C only minimally affected the amount of thrombin generated.
When endothelial cells were the tissue factor source with platelets
providing the surface for thrombin generation, activated protein C did
increase the time until the burst of thrombin generation but had
minimal effects on the total amount of thrombin generated. Activated
protein C had essentially no effect on thrombin generation when
monocytes were the tissue factor source with platelets providing the
surface for thrombin generation. From the studies reported here, we
conclude that in vivo, despite the important role of the protein C
system in regulating thrombosis, activated protein C does not serve as
a primary regulator of platelet-dependent thrombin generation.
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