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Estrogen stimulates von Willebrand factor production by cultured
endothelial cells
RL Harrison and PA McKee
Monolayers of cultured human umbilical vein endothelial cells were exposed
to 17 beta-estradiol and compared to control cultures with respect to
levels of von Willebrand factor (vWF) released into the media after 3-5
days of incubation. The amount of functional vWF activity was assessed by
ristocetin-induced platelet aggregation and by a radioreceptor platelet
assay. vWF antigen was quantitated by immunoassay. The DNA content of each
monolayer was determined fluorometrically and used as a measure of cell
number. By all assays, vWF levels in the media from the estradiol-treated
endothelial cells were reproducibly and significantly higher when compared
with control values. The amount of vWF produced by the cultured endothelial
cells showed a dose-response effect to the estradiol added to the media.
The estradiol-treated cells produced approximately 1.3 +/- 0.30 micrograms
vWF/ml/micrograms DNA at 2 ng estradiol/ml, compared with control cultures
that produced 0.75 +/- 0.16 microgram vWF/ml/micrograms DNA (p less than
0.001). The estradiol-treated monolayers consistently contained slightly
greater amounts of DNA than control cultures: 2.0 +/- 0.10 micrograms
versus 1.7 +/- 0.12 micrograms DNA (p less than 0.001). By multivariant
analysis, however, the differences in cell number could only account for
less than or equal to 10% of the elevation in the level of vWF that
occurred in response to estradiol. By SDS-agarose electrophoresis and
radioimmunoblotting, the vWF within the cytosol of the endothelial cells
was found to possess a multimeric pattern similar to that found for either
purified plasma vWF or vWF released into media overlying endothelial cell
cultures. Our studies indicate that estrogen directly stimulates
endothelial cells to increase their rate of production of vWF and, in
addition, causes a slight increase in endothelial cell replication. These
data may bear on the observation that administration of estrogen to some
women with von Willebrand's disease causes an increase in their functional
levels of vWF.
Volume 63,
Issue 3,
pp. 657-664,
03/01/1984
Copyright © 1984 by The American Society of Hematology

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