title: Endothelial ephrin-B2 is essential for arterial vasodilation in mice.
abstract: OBJECTIVE
  The cell surface protein ephrin-B2 is expressed in arterial and not venous ECs throughout development and adulthood. Endothelial ephrin-B2 is required for vascular development and angiogenesis, but its role in established arteries is currently unknown. We investigated the physiological role of ephrin-B2 signaling in adult endothelium.
  
  
  METHODS
  We generated adult conditional knockout mice lacking the Efnb2 gene specifically in ECs and evaluated the vasodilation responses to blood flow increase and ACh in the cremaster muscle preparation by intravital microscope and in carotid artery by in vivo ultrasound.
  
  
  RESULTS
  We found that the Efnb2 conditional knockout mice were defective in acute arterial dilation. Vasodilation was impaired in cremaster arterioles in response to either increased flow or ACh, and in the carotid arteries in response to increased flow. Levels of cGMP, an effector of NO, were diminished in mutant arteries following ACh stimulation. GSNO, a donor for the vasodilator NO, alleviated the vasodilatory defects in the mutants. Immunostaining showed that a subset of ephrin-B2 proteins colocalized with caveolin-1, a negative regulator of eNOS.
  
  
  CONCLUSIONS
  Our data suggest that endothelial ephrin-B2 is required for endothelial-dependent arterial dilation and NO signaling in adult endothelium.
authors.affiliation: Laboratory for Accelerated Vascular Research, Division of Vascular Surgery, Department of Surgery, University of California, San Francisco, California, USA.
authors.forename: Yuankai
authors.initials: Y
authors.lastname: Lin
authors.forename: Weiya
authors.initials: W
authors.lastname: Jiang
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ng
authors.forename: Asmita
authors.initials: A
authors.lastname: Jina
authors.forename: Rong A
authors.initials: RA
authors.lastname: Wang
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000502:physiology*; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D017536:Carotid Artery, Common / Q000502:physiology; D051242:Caveolin 1 / Q000032:analysis; D006152:Cyclic GMP / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D036388:Ephrin-B2 / Q000502:physiology*; D005260:Female; D017930:Genes, Reporter; D018056:Hemorheology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000098:blood supply; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009928:Organ Specificity; D026422:S-Nitrosoglutathione / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D051242:Caveolin 1; D036388:Ephrin-B2; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D006152:Cyclic GMP; D000109:Acetylcholine
keywords: angiogenesis; ephrin; nitric oxide; vascular biology