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Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 93 No. 8 (April 15), 1999: pp. 2627-2636 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, and Franco Dammacco From the Institute of Human Anatomy, Histology and Embryology, and the Department of Biomedical Sciences and Human Oncology, University of Bari School of Medicine, Bari, Italy; and the Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia School of Medicine, Brescia, Italy. Hematopoietic 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 Janus Kinase-2 (JAK-2) phosphorylation, cell proliferation, and matrix metalloproteinase-2 (MMP-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 it 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Schroder, A. Kohnen, A. Aicher, E. A. Liehn, T. Buchse, S. Stein, C. Weber, S. Dimmeler, and R. P. Brandes NADPH Oxidase Nox2 Is Required for Hypoxia-Induced Mobilization of Endothelial Progenitor Cells Circ. Res., September 11, 2009; 105(6): 537 - 544. [Abstract] [Full Text] [PDF] H. Rundqvist, E. Rullman, C. J. Sundberg, H. Fischer, K. Eisleitner, M. 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