Abstract 654: Endothelial Ephrin-B2 Essential for Arterial Vasodilation is also Required for Acute Ischemic Recovery

Abstract

Rationale: The cell surface protein ephrin-B2 is expressed in arterial and not venous endothelial cells throughout development and adulthood. We have recently reported that endothelial ephrin-B2 is essential in acute arterial vasodilation. Here we proposed that endothelial ephrin-B2 plays important protective roles against acute ischemia. Objective: We investigated the role of endothelial ephrin-B2 following experimental hindlimb ischemia in mice lacking ephrin-B2 specifically in the endothelium. Methods and Results: We performed femoral artery occlusion in mice lacking the ephrin-B2 gene specifically in endothelial cells. We found that the mutant mice exhibited lower residual blood flow than controls immediately following the surgical occlusion by laser doppler perfusion imaging. The mutant mice also developed gangrene not seen in controls soon after the occlusion. Histologically the tissue regeneration and recovery were impaired in the hindlimb of the mutant mice. S-nitrosoglutathione, a donor for nitric oxide, alleviated the perfusion impairment immediately after the occlusion and improved the tissue survival and recovery in the mutants to levels comparable to those in controls. We further demonstrated that acetylcholine-stimulated nitric oxide production was impaired in ephrin-B2 mutant aortae, detected by both chemiluminescence that measures NOx and electron spin resonance that measures bioavailable NO. Conclusions: Our data demonstrate that mice lacking ephrin-B2 in endothelial cells are defective in acute ischemic recovery after femoral artery occlusion. Our data also suggest that endothelial ephrin-B2 could potentially interact with the nitric oxide pathway that is critical in its function in arterial dilation and protection against ischemia.