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In-Depth Information
Chapter 15
In Vivo Angiogenic Activity of Erythropoietin
Domenico Ribatti
Abstract
The role of erythropoietin (Epo) has been demonstrated in tissues outside the hematopoietic system,
including the cardiovascular system, where Epo promotes various effects in endothelial cells. Here, we
have demonstrated the angiogenic capacity of recombinant human Epo (rhuEpo) in vivo, by means of the
chick embryo chorioallantoic membrane (CAM) assay, a well-established in vivo assay to study angiogen-
esis and antiangiogenesis.
Key words
Angiogenesis, Chorioallantoic membrane, Erythropoietin
1
Introduction
The role of erythropoietin (Epo) has been demonstrated in tissues
outside the hematopoietic system, including the cardiovascular
system, where Epo promotes various effects in endothelial cells.
Epo stimulates both proliferation and migration of human and
bovine endothelial cells in vitro and of endothelial cells isolated
from rat mesentery (
1-4
), as well as in the rat aortic ring model (
5
).
Moreover, Epo induces endothelin-1 (ET-1) expression in endothe-
lial cell cultures (
5, 6
). Recombinant human Epo (rHuEpo) induces
an increased cell proliferation, matrix metalloproteinase-2 (MMP-2)
expression, and differentiation into vascular tubes of human
endothelial cells in vitro (
1
). Epo receptor (EpoR) mRNA is
expressed in human umbilical vein endothelial cells (HUVEC),
bovine adrenal capillaries, and rat brain capillaries (
2, 3
).
Epo and EpoR are expressed in the vasculature during embryo-
genesis and their deletion in null embryos leads to angiogenic
defects, whereas vasculogenesis was not affected, consistent with
the differential expression of Epo and EpoR during the early stages
of embryonic development (
7
).
RhuEpo increases also the number of circulating endothelial
cells and endothelial precursor cells (EPC) in preclinical models (
8
)
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