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]
BM Ewenstein, A Inbal, JS Pober and RI Handin
Hematology Division, Brigham and Women's Hospital, Boston, MA 02115.
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.
Volume 75,
Issue 7,
pp. 1466-1472,
04/01/1990
Copyright © 1990 by The American Society of Hematology
