Human erythropoietin induces a pro-angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo

被引:462
作者
Ribatti, D
Presta, M
Vacca, A
Ria, R
Giuliani, R
Dell'Era, P
Nico, B
Roncali, L
Dammacco, F
机构
[1] Univ Bari, Sch Med, Inst Human Anat Histol & Embryol, I-70124 Bari, Italy
[2] Univ Bari, Sch Med, Dept Biomed Sci & Human Oncol, I-70124 Bari, Italy
[3] Univ Brescia, Sch Med, Dept Biomed Sci & Biotechnol, Brescia, Italy
关键词
D O I
10.1182/blood.V93.8.2627.408k21_2627_2636
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (C) 1999 by The American Society of Hematology.
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页码:2627 / 2636
页数:10
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