ACUTE VON-WILLEBRAND-FACTOR SECRETION FROM THE ENDOTHELIUM IN-VIVO - ASSESSMENT THROUGH PLASMA PROPEPTIDE (VWF-AGII) LEVELS

Elevated plasma concentrations of von Willebrand factor (vWf) are incr easingly recognized as a cardiovascular risk factor, and are used as a marker of endothelial activation. However, the factors which determin e the rate of vWf release from the endothelium in vivo have not been d efined clearly. In addition, vWf plasma levels may also be influenced by adhesion of vWf to the vascular wall or to platelets, and by its ra te of degradation. The propeptide of vWf (also called vWf:AgII) is sto red and released in equimolar amounts with vWf. In the present study w e attempted to determine whether this propeptide could be a more relia ble marker of endothelial secretion than vWf itself. To accomplish thi s we developed an ELISA based on monoclonal antibodies. The propeptide levels in normal plasma were found to be 0.7 mu g/ml, more than 10 ti mes lower than vWf itself. Administration of desmopressin (DDAVP) indu ced a rapid relative increase in propeptide (from 106 to 879%) and in vWf (from 112 to 272%). However, the increases in vWf and propeptide w ere equivalent when expressed in molar unit's. A time course study ind icated a half-life of the propeptide of 3 h or less. In a baboon model of disseminated intravascular coagulation (DIC) induced by FXa, vWf i ncreased by less than 100%, whereas the propeptide concentrations incr eased by up to 450%. In view of the massive thrombin generation (as as sessed by fibrinogen depletion), the increases in vWf are small, compa red 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 endo thelial secretion.