Quantitative analysis of von Willebrand factor propeptide release in vivo: Effect of experimental endotoxemia and administration of 1-deamino-8-D-arginine vasopressin in humans

被引:178
作者
Borchiellini, A
Fijnvandraat, K
tenCate, JW
Pajkrt, D
vanDeventer, SJH
Pasterkamp, G
MeijerHuizinga, F
ZwartHuinink, L
Voorberg, J
vanMourik, JA
机构
[1] NETHERLANDS RED CROSS,BLOOD TRANSFUS SERV,CENT LAB,DEPT BLOOD COAGULAT,NL-1066 CX AMSTERDAM,NETHERLANDS
[2] UNIV AMSTERDAM,ACAD MED CTR,CTR HEMOSTASIS THROMBOSIS ATHEROSCLEROSIS & INFLA,NL-1105 AZ AMSTERDAM,NETHERLANDS
[3] UNIV AMSTERDAM,ACAD MED CTR,DEPT EXPT INTERNAL MED,NL-1105 AZ AMSTERDAM,NETHERLANDS
关键词
D O I
10.1182/blood.V88.8.2951.bloodjournal8882951
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The results of studies with cultured endothelial cells have shown that most von Willebrand factor (VWF) synthesized is directly secreted (constitutive pathway) and consists of both mature vWF, its precursor molecule pro-vWF, and the cleaved vWF prosequence. Only fully processed, functionally mature vWF is stored within the cell, together with the propeptide, and leaves the cell only on stimulation (regulated secretion). Both in resting and stimulated cultured endothelial cells, the stoichiometry of the released propeptide to the released mature vWF is essentially equimolar. In the present study, we have measured the molar ratio of propeptide to mature vWF in vivo, both under resting conditions and conditions that reflect activation of the endothelium. To this end, we devised a method that allows the measurement of the propeptide (vW antigen II) on a quantitative, ie, molar basis, using purified recombinant propeptide as a standard. Our results show that the molar concentration of the propeptide in normal plasma is about one tenth of the concentration of mature vWF (expressed as half-dimer concentration), This ratio is approximately 1:1 in the medium of cultured endothelial cells, On administration in healthy subjects of either 1-deamino-8-D-arginine vasopressin or endotoxin, both agents being known to elicit an intravascular increase of vWF, the molar ratio of propeptide to mature vWF increased fourfold to fivefold. The propeptide concentration returned to baseline values after about 6 to 7 hours of injection of each stimulus, whereas the increase of mature vWF was much more sustained. Because the respective half-lives of mature vWF and its propeptide clearly differ, measurement of the concentration of these proteins could provide a means to assess the extent of activation of the endothelium under physiological and pathophysiological conditions. (C) 1996 by The American Society of Hematology.
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页码:2951 / 2958
页数:8
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