HUMAN ERYTHROPOIETIN INDUCES A PRO-ANGIOGENIC PHENOTYPE IN CULTURED ENDOTHELIAL CELLS AND STIMULATES NEOVASCULARIZATION IN VIVO 

 

Domenico Ribatti, Marco Presta, Angelo Vacca, Roberto Ria, Roberta Giuliani, Patrizia Dell’Era, Beatrice Nico, Luisa Roncali, Franco Dammacco

Institute of Anatomy, Histology and Embryology [D.R., B.N., L.R.] and Department of Biomedical Sciences and Human Oncology [A.V., R.R., F.D.], University of Bari, Piazza G. Cesare 11, 70124 Bari; Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, via Valsabbina 19, 25123 Brescia, Italy [M.P., R.G.,  P.D.’E.].
 

 
 

Complex Between The Extracellular Domain Of Erythropoietin (Epo) Receptor [Ebp] And An Agonist Peptide [Emp1]
 
 
 

3D structure of EpoR



If the plug-in named ChemScape Chime is properly installed on your computer, you should see a rotating 3D EpoR molecule. The molecule can be moved by clicking it with the left button of your mouse and its characteristics, including automatic rotation, can be modified by clicking it with the right button. 

To download the plug-in:. 
 
 



Back to: Presta's lab

 

 ABSTRACT

Hemopoietic and endothelial cell lineages share common progenitors. Accordingly, cytokines formerly thought to be specific for the hematopoietic system have been shown to affect several functions in endothelial cells, including angiogenesis. In this study, we investigated the angiogenic potential of erythropoietin (Epo), the main hormone regulating proliferation, differentiation, and survival of erythroid cells. 

Epo receptors (EpoRs) have been identified in the human EA.hy926 endothelial cell line by Western blot analysis. Also, recombinant human Epo (rHuEpo) stimulates JAK-2 phosphorylation, cell proliferation, and matrix metalloproteinases-2 production in EA.hy926 cells, and significantly enhances their differentiation into vascular structures when seeded on Matrigel. 

In vivo, rHuEpo induces a potent angiogenic response in the chick embryo chorioallantoic membrane (CAM). Accordingly, endothelial cells of the CAM vasculature express EpoRs, as shown by immunostaining with an anti-EpoR antibody. The angiogenic response of CAM blood vessels to rHuEpo was comparable to that elicited by the prototypic angiogenic cytokine basic fibroblast growth factor (FGF2), it occurred in the absence of a significant mononuclear cell infiltrate, and was not mimicked by endothelin-1 (ET-1) treatment. 

Taken together, these data demonstrate the ability of Epo to interact directly with endothelial cells and to elicit an angiogenic response in vitro and in vivo, and thus act as  a "bona fide" direct angiogenic factor.
 
 
 

Blood. 1999 Apr 15;93(8):2627-36.

 

Back to: AIRC - Special Project Angiogenesis