|
|
 Previous Article | Table of Contents | Next Article 
Clearance of normal and type 2A von Willebrand factor in the rat
JH Stoddart , J Andersen and DC Lynch
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115,
USA.
A model for the in vivo clearance of normal and mutant forms of human von
Willebrand factor (vWF) has been established using catheterized rats. vWF
clearance rates in rat plasma were determined by quantitation of reduced
vWF subunits on sodium dodecyl sulfate-polyacrylamide gel electrophoresis
(SDS-PAGE), and multimeric vWF was analyzed using nondenaturing SDS-agarose
gels. Normal vWF derived from human umbilical vein endothelial cells
displayed a biphasic pattern of clearance, with half times of 35 minutes (T
1/2 a; SD 15. min.) and 245 minutes (T 1/2 b; SD 76. min.); metabolic
clearance rate = 0.65%/minute. High molecular weight multimers of vWF were
cleared more rapidly than dimeric vWF. vWF containing the S1613P mutation
found in some type 2A von Willebrand disease (vWD) patients was observed to
undergo proteolysis in vivo resulting in a reduction of high molecular
weight vWF and concomitant appearance of rapidly-migrating satellite
species, although the overall clearance rate of vWF antigen was similar to
wild type vWF. These results provide direct in vivo evidence that the
S1613P mutation causes the characteristic type 2A vWD phenotype.
Full-length recombinant vWF produced from transfected Chinese hamster ovary
cells was cleared at a similar rate to endothelial cell-derived vWF, and
recombinant vWF devoid of O-linked carbohydrates was cleared significantly
faster. vWF devoid of sulfate was cleared at a similar rate as wild type
vWF, indicating the sulfate moiety of vWF does not regulate in vivo
clearance. This animal model should prove useful in subsequent in vivo
analysis of additional forms of vWD and in the development of protease
inhibitor therapy for 2A vWD.
Volume 88,
Issue 5,
pp. 1692-1699,
09/01/1996
Copyright © 1996 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
C. J. M. van Schooten, C. V. Denis, T. Lisman, J. C. J. Eikenboom, F. W. Leebeek, J. Goudemand, E. Fressinaud, H. M. van den Berg, P. G. de Groot, and P. J. Lenting
Variations in glycosylation of von Willebrand factor with O-linked sialylated T antigen are associated with its plasma levels
Blood,
March 15, 2007;
109(6):
2430 - 2437.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Lenting, E. Westein, V. Terraube, A.-S. Ribba, E. G. Huizinga, D. Meyer, P. G. de Groot, and C. V. Denis
An Experimental Model to Study the in Vivo Survival of von Willebrand Factor: BASIC ASPECTS AND APPLICATION TO THE R1205H MUTATION
J. Biol. Chem.,
March 26, 2004;
279(13):
12102 - 12109.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. W. Kamphuisen, J. C. J. Eikenboom, and R. M. Bertina
Elevated Factor VIII Levels and the Risk of Thrombosis
Arterioscler Thromb Vasc Biol,
May 1, 2001;
21(5):
731 - 738.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. L. Turecek, H. Gritsch, L. Pichler, W. Auer, B. Fischer, A. Mitterer, W. Mundt, U. Schlokat, F. Dorner, H. J. M. Brinkman, et al.
In Vivo Characterization of Recombinant von Willebrand Factor in Dogs With von Willebrand Disease
Blood,
November 1, 1997;
90(9):
3555 - 3567.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
