Summary
Elevated plasma concentrations of von Willebrand factor (vWf) are increasingly recognized
as a cardiovascular risk factor, and are used as a marker of endothelial activation.
However, the factors which determine the rate of vWf release from the endothelium
in vivo have not been defined clearly. In addition, vWf plasma levels may also be
influenced by adhesion of vWf to the vascular wall or to platelets, and by its rate
of degradation. The propeptide of vWf (also called vWf:AgII) is stored and released
in equimolar amounts with vWf. In the present study we attempted to determine whether
this propeptide could be a more reliable marker of endothelial secretion than vWf
itself. To accomplish this we developed an ELISA based on monoclonal antibodies. The
propeptide levels in normal plasma were found to be 0.7 µg/ml, more than 10 times
lower than vWf itself. Administration of desmopressin (DDAVP) induced a rapid relative
increase in propeptide (from 106 to 879%) and in vWf (from 112 to 272%). However,
the increases in vWf and propeptide were equivalent when expressed in molar units.
A time course study indicated a half-life of the propeptide of 3 h or less. In a baboon
model of disseminated intravascular coagulation (DIC) induced by FXa, vWf increased
by less than 100%, whereas the propeptide concentrations increased by up to 450%.
In view of the massive thrombin generation (as assessed by fibrinogen depletion),
the increases in vWf are small, compared to the strong secretory response to thrombin
and fibrin previously observed in vitro. Our results suggest that due to its rapid
turnover, the propeptide could provide a sensitive plasma marker of acute endothelial
secretion.
