Published Online
on April 25, 2005

A more recent version of this article appeared on May 3, 2005

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Submitted on June 27, 2004
Revised on November 5, 2004
Accepted on December 8, 2004

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, and Douglas W. Losordo MD

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

^* To whom correspondence should be addressed. E-mail: shin559182{at}aol.com.

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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