Vischer U M, Ingerslev J, Wollheim C B, Mestries J C, Tsakiris D A, Haefeli W E, Kruithof E K
Division de Biochimie Clinique, HCUG, Geneva, Switzerland.
Thromb Haemost. 1997 Feb;77(2):387-93.
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 microgram/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.
血管性血友病因子（vWf）的血浆浓度升高日益被视为一种心血管危险因素，并用作内皮激活的标志物。然而，体内决定vWf从内皮释放速率的因素尚未明确界定。此外，vWf的血浆水平还可能受vWf与血管壁或血小板的黏附及其降解速率的影响。vWf的前肽（也称为vWf:AgII）与vWf以等摩尔量储存和释放。在本研究中，我们试图确定该前肽是否可能是比vWf本身更可靠的内皮分泌标志物。为实现这一目标，我们开发了一种基于单克隆抗体的酶联免疫吸附测定（ELISA）。发现正常血浆中的前肽水平为0.7微克/毫升，比vWf本身低10倍以上。给予去氨加压素（DDAVP）可导致前肽迅速相对增加（从106%增至879%）以及vWf增加（从112%增至272%）。然而，以摩尔单位表示时，vWf和前肽的增加是相当的。一项时间进程研究表明前肽的半衰期为3小时或更短。在由FXa诱导的弥漫性血管内凝血（DIC）狒狒模型中，vWf增加不到100%，而前肽浓度增加高达450%。鉴于大量凝血酶生成（通过纤维蛋白原消耗评估），与先前在体外观察到的对凝血酶和纤维蛋白的强烈分泌反应相比，vWf的增加较小。我们的结果表明，由于其快速周转，前肽可为急性内皮分泌提供一个敏感的血浆标志物。
