Von Willebrand Factor: Biological Function and Molecular Defects

Abstract Endothelial cells were cultured from the umbilical veins of two neonates with type I von Willebrand disease (vWD) and compared with cells cultured in parallel from normal control umbilical veins. In both cases, cultured vWD endothelial cells contained less messenger RNA (mRNA) encoding von Willebrand factor (vWF), and constitutively secreted two- to fourfold less vWF protein than their matched controls. Regulated secretion of stored vWF induced by thrombin or phorbol-12- myristate-13-acetate (PMA) was also diminished in vWD cells. Both the mRNA and protein produced by each of these type I vWD cells appeared to be of normal size. However, despite the diminished size of the vWF storage pool, electron microscopy of endothelial cells in situ showed normal appearing vWF storage organelles (Weibel-Palade bodies). These studies show that cultured umbilical vein endothelial cells can be used to explore the molecular defects in type I and perhaps other forms of vWD, and suggest that at least some forms of type I vWD are caused by diminished mRNA transcription or subsequent translation due to a defective vWF allele.

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Isolated Molecular Defects of von Willebrand Factor Binding to Collagen do not correlate with Bleeding Symptoms

32nd Hemophilia Symposium Hamburg 2001 ◽

10.1007/978-3-642-18150-4_17 ◽

2003 ◽

pp. 127-130

Author(s):

R. Schneppenheim ◽

T. Obser ◽

E. Drewke ◽

U. Gross-Wieltsch ◽

E. G. Huizinga ◽

...

Keyword(s):

Von Willebrand Factor ◽

Molecular Defects ◽

Factor Binding ◽

Von Willebrand ◽

Willebrand Factor

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von Willebrand factor sialylation—A critical regulator of biological function

Journal of Thrombosis and Haemostasis ◽

10.1111/jth.14471 ◽

2019 ◽

Vol 17 (7) ◽

pp. 1018-1029 ◽

Cited By ~ 8

Author(s):

Soracha Ward ◽

Jamie M. O'Sullivan ◽

James S. O'Donnell

Keyword(s):

Von Willebrand Factor ◽

Biological Function ◽

Von Willebrand ◽

Willebrand Factor

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Molecular studies of von Willebrand disease: reduced von Willebrand factor biosynthesis, storage, and release in endothelial cells derived from patients with type I von Willebrand disease [published erratum appears in Blood 1990 Nov 1;76(9):1901]

Blood ◽

10.1182/blood.v75.7.1466.bloodjournal7571466 ◽

1990 ◽

Vol 75 (7) ◽

pp. 1466-1472

Author(s):

BM Ewenstein ◽

A Inbal ◽

JS Pober ◽

RI Handin

Keyword(s):

Endothelial Cells ◽

Von Willebrand Factor ◽

Messenger Rna ◽

Umbilical Vein ◽

Von Willebrand Disease ◽

Type I ◽

Molecular Defects ◽

Umbilical Vein Endothelial Cells ◽

Von Willebrand ◽

Willebrand Factor

Endothelial cells were cultured from the umbilical veins of two neonates with type I von Willebrand disease (vWD) and compared with cells cultured in parallel from normal control umbilical veins. In both cases, cultured vWD endothelial cells contained less messenger RNA (mRNA) encoding von Willebrand factor (vWF), and constitutively secreted two- to fourfold less vWF protein than their matched controls. Regulated secretion of stored vWF induced by thrombin or phorbol-12- myristate-13-acetate (PMA) was also diminished in vWD cells. Both the mRNA and protein produced by each of these type I vWD cells appeared to be of normal size. However, despite the diminished size of the vWF storage pool, electron microscopy of endothelial cells in situ showed normal appearing vWF storage organelles (Weibel-Palade bodies). These studies show that cultured umbilical vein endothelial cells can be used to explore the molecular defects in type I and perhaps other forms of vWD, and suggest that at least some forms of type I vWD are caused by diminished mRNA transcription or subsequent translation due to a defective vWF allele.

Download Full-text