Abstract 511: Ephrin-B2 Is Essential for Ischemic Recovery following Femoral Artery Occlusion in Mice
The cell surface protein ephrin-B2 is expressed in arterial and not venous endothelial cells in adulthood mice. The role for ephrin-B2 in adult vascular physiology is currently unknown. We have recently reported that endothelial ephrin-B2 is essential in acute arterial vasodilation. Here we report that endothelial ephrin-B2 plays important protective roles against acute ischemia. We investigated the role of endothelial ephrin-B2 following experimental femoral artery occlusions in mice lacking ephrin-B2 specifically in the endothelium. Mutant mice exhibited lower foot blood flow by laser doppler perfusion imaging and developed gangrene not seen in controls, following femoral arterial occlusions. Histologically, neovascularization and muscle regeneration were impaired in the mutant hindlimb. S-nitrosoglutathione, a donor for nitric oxide, improved the foot blood flow and tissue survival in the mutants after the occlusion. Mechanistically, we demonstrated that acetylcholine-stimulated nitric oxide production was impaired in ephrin-B2 mutant, detected by both chemiluminescence that measures NO metabolites and electron spin resonance that measures bioavailable NO. Our data demonstrate that mice lacking ephrin-B2 in endothelial cells are defective in acute ischemic recovery after femoral artery occlusion and suggest that endothelial ephrin-B2 may interact with the nitric oxide pathway to mediate arterial dilation and ischemia protection.
Author Disclosures: R.A. Wang: None. Y. Lin: None. W. Jiang: None. J. Youn: None. W. Gong: None. J.R. Fineman: None. A.W. Bollen: None. H. Cai: None.
- © 2015 by American Heart Association, Inc.