To further ascer- tam the putative mechanisms involved in the induction by. rhEPO of increased expression of VEGF receptor. mRNA, experiments similar.
J Am
Role of Vascular Erythropoietin-Related
Endothelial Growth Factor on Endothelial Cell Proliferation
MARIA VICTORIA ALVAREZ ARROYO, MARIA ANGELES FRANCISCO ROMAN GONZALEZ PACHECO, DUNYONG SANTOS CASADO, and CARLOS CARAMELO Instituto
de
Nephrol 9: 1998-2004, 1998
Soc
Investigaciones
M#{233}dicas,
Fundaci#{243}n
Jim#{233}nez DIaz,
CASTILLA, TAN, AMPARO
Universidad
Aut#{243}noma
RIESCO,
de Madrid,
Madrid,
Spain.
Abstract.
The
poietin
(rhEPO)
standing
of
vascular
rhEPO
action
of
BAEC presence
proliferation of fetal
as
rhEPO-related
BAEC
of a positive
Erythropoietin
vascular
cellular
involve
the
induction use
rhEPO
and
factor
for
of erythropoietin
muscle,
the effects
and
and
by of
number
of cell
VEGF
of eryhave
cells
36
we
receptors
BAEC
pretreatment
both
KDR/fik-
of the
functional mopoietic factor, VEGF
and
processes
effect
mechanisms
triggering
VEGF
(9-i
of an
probably
related
genetic
fore,
to similarities
programming
that
(8).
erythropoietin
The
might
common
in the
embryo!ogic
hypothesis
can
resemble
be
elements, origin raised,
on endothelial
and
marrow
series
etin
and
tor etin
October
Correspondence
24, 1997. Accepted to Dr. Carlos
Caramelo,
Fundaci#{243}nJim#{233}nez DIaz, Universidad cos
2. 28040
Madrid,
1046-6673/0901 Journal Copyright
April
10, 1998.
Instituto
Aut#{243}nomade Madrid,
Spain.
1 - 1998$03.00/0
of the 0
American 1998
by the
Society American
Cat#{243}li-
VEGF
on
of Nephrology
an important action
several
issue
as
an
common
addition,
of
maturation,
endoaspects
erythropoietin
described
including
erythropoietin
and
through
These
interaction
both
a recently
to be conveyed
features
between
the
role
in
the
erythroid
VEGF
intracel-
tyrosine
kinase-
together
effects
make
the
of erythropoi-
likely. are insufficient of et
human
shown
vascular
it has been
concerning
erythropoietin
a!. have
a tyrosine
on that
the effects
endothelial
cells
phosphoryiation-related
suggested
that
the precise
endothelia!
Re-
of erythropoiwere
pathway
endothelin-i
effec-
cells.
mediated (18).
(ET-i)
In
might
be a mediator for rhEPO-induced endothelial cell proliferation, although a precise signal transduction sequence has not been identified
of Nephrology Society
Av Reyes
M#{233}dicas,
and
as a treatment.
rhEPO
has
(14-17).
however, Hailer
through
de Investigaciones
appear
mechanisms
cently, Received
of
study and
between rhEPO in neovascuiarization
production
(3) both
and
signals
Data, its
VEGF
predominantly heand an angiogenic
rhEPO
regard,
VEGF
precursor
(12,13);
lular
there-
cells
basis
between
Accordingly,
the
1); (2)
existence
several
receiving
In this
Both
share
interactions
relationship importance
conditions
liferation.
processes
of
a structural
exist between rhEPO and vascular endothelial growth factor (VEGF), as follows: (1) relevant similarities exist between the and
pro-
the expression
providing
a hormone with erythropoietin,
the
pathways
cell
between namely,
factor.
mediated
endotheliai
VEGF that
identified in the present level of mRNA expression
precursors.
in both
and
of the disclosed
inhibition by genistein suggests that was involved in the VEGF receptor
in patients
growth
Ca2
M) in BAEC = 704 ± 111
0.01). To further of VEGF effect by
