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(Circulation Research. 2007;100:599.)
© 2007 American Heart Association, Inc.

Editorials

Switching on Reparative Angiogenesis

Essential Role of the Vascular Erythropoietin Receptor

Paolo Madeddu, Costanza Emanueli

From the Chair of Experimental Cardiovascular Medicine (P.M., C.E.), Bristol Heart Institute, University of Bristol, United Kingdom.

Correspondence to Paolo Madeddu, Bristol Heart Institute, University of Bristol, Level 7, Bristol Royal Infirmary, Upper Maudlin Street, Bristol BS2 8HW, UK. E-mail madeddu@yahoo.com

See related article, pages 662–669

Key Words: limb ischemia • angiogenesis • vasculogenesis • endothelial progenitor cells • migration

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Neovascularization and hematopoiesis are parts of an integrated and tightly regulated program aimed at creating the logistics for the delivery of cells, oxygen, and nutrients to the different organs of the body. This cooperation starts during the early stages of development, with endothelial and hematopoietic cells emerging in temporal and spatial proximity, in both the embryo and the extraembryonic yolk sac. During adulthood, hematopoiesis takes place mainly in the bone marrow (BM), where hematopoietic stem cells (HSC) reside in a specialized microenvironment, the "stem cell niche," which provides the optimal conditions for stem cell maintenance. Here too, HSC and endothelial progenitor cells (EPC) seem to be closely related, to such an extent that the distinction between these cells remains shadowy. For instance, the subset of CD34⁺ BM cells that coexpress the receptor for vascular endothelial growth factor, VEGFR2, is enriched for both HSC and endothelial precursors in mice and humans.^1–3 Single CD34⁺VEGFR2⁺ cells from adult BM generate both hematopoietic and endothelial cells in vitro and have long-term proliferative capacity.⁴ When injected into the hindlimb muscles of immunodeficient SCIDbg mice, these hematopoietic CD34⁺VEGFR2⁺ cells accelerate the recovery from limb ischemia through stimulation of neovascularization and myogenesis.⁵

Additionally, integration of hematopoiesis and angiogenesis is supported by hormones, cytokines and growth factors. Erythropoietin (Epo) stimulates the proliferation of erythroid precursors and their differentiation into mature red cells,⁶ and also exerts in vivo proangiogenic and reendothelialization actions, through activation of PI3K/nitric oxide-dependent EPC mobilization.^7,8 Accordingly, circulating Epo has been shown to be . . . [Full Text of this Article]

Related Article:

Important Role of Erythropoietin Receptor to Promote VEGF Expression and Angiogenesis in Peripheral Ischemia in Mice

Makoto Nakano, Kimio Satoh, Yoshihiro Fukumoto, Yoshitaka Ito, Yutaka Kagaya, Naoto Ishii, Kazuo Sugamura, and Hiroaki Shimokawa
Circ. Res. 2007 100: 662-669. [Abstract] [Full Text] [PDF]