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(Circulation. 2005;111:2210-2218.)
© 2005 American Heart Association, Inc.

Vascular Medicine

Functional Ephrin-B2 Expression for Promotive Interaction Between Arterial and Venous Vessels in Postnatal Neovascularization

Shin-ichiro Hayashi, MD, PhD; Takayuki Asahara, MD, PhD; Haruchika Masuda, MD, PhD; Jeffrey M. Isner, MD; Douglas W. Losordo, MD

From the Division of Cardiovascular Research and Medicine, St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass.

Correspondence to Shin-ichiro Hayashi, MD, PhD, St Elizabeth’s Medical Center, Tufts University School of Medicine, 736 Cambridge St, Boston, MA 02135. E-mail shin559182{at}aol.com

Received June 27, 2004; revision received November 5, 2004; accepted December 8, 2004.

Background— Ephrin-B2, one of the transmembrane ligands, is a genetic marker of arterial endothelial cells (ECs) at embryonic stages and is essential for cardiovascular development, but its roles in ischemic cardiovascular disease are not well understood. In this study, we focused on the function of ephrin-B2 in postnatal neovascularization.

Methods and Results— We found that ephrin-B2 is exclusively expressed and significantly upregulated in the arterial vasculature after the initial angiogenic responses in tissue ischemia. Upregulation of ephrin-B2 is also observed in EC cordlike formation in vitro. Interestingly, ephrin-B2 expression on ECs was enhanced by promotive angiogenic growth factors, such as vascular endothelial growth factor, basic fibroblast growth factor, and hepatocyte growth factor, whereas it was attenuated by angiopoietin-1, a factor for blood vessel maturation. Moreover, an ephrin-B2–rich environment was shown to induce neovascularization mainly through venous angiogenesis in an in vivo cornea micropocket assay.

Conclusions— Our study indicates that the ephrin-B2 ligand is likely to have functional expression on angiogenic arterial ECs and induce a subsequent promotive effect on venous vessels during postnatal neovascularization.

Key Words: ischemia • ephrin-B2 • angiogenesis, postnatal • endothelial cells

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