title: Notch-dependent regulation of the ischemic vasodilatory response--brief report.
abstract: OBJECTIVE
  We have recently described that Notch activates nitric oxide (NO) signaling in the embryonic endocardium. Both Notch signaling and NO signaling have been shown to be important during adult arteriogenesis. Notch has been shown to be required for remodeling of the collateral vessels, whereas NO is required for the initial vasodilatory response to ischemia. Whether Notch also has an impact on the vasodilatory phase of arteriogenesis after ischemia is not known. We tested the hypothesis that endothelial cell-Notch function is required for NO induction and vasodilation, in response to ischemia in the adult vasculature.
  
  
  RESULTS
  We observed a significant decrease in NO levels in the dorsal aorta using a mouse model where Notch was inhibited in endothelial cell in a Tet-inducible fashion. In a femoral artery ligation model, inhibition of endothelial cell-Notch reduced reperfusion and NO generation, as quantified by laser Doppler perfusion imaging and by phosphoendothelial NO synthase, nitrotyrosine, and phosphovasodilator-stimulated phosphoprotein staining, respectively.
  
  
  CONCLUSIONS
  Endothelial Notch activation is required for NO production and reactive vasodilation in a femoral artery ligation model.
authors.affiliation: Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, V5Z 1L3, Canada.
authors.forename: Alex C Y
authors.initials: AC
authors.lastname: Chang
authors.forename: Alexandre
authors.initials: A
authors.lastname: Patenaude
authors.forename: Katherine
authors.initials: K
authors.lastname: Lu
authors.forename: Megan
authors.initials: M
authors.lastname: Fuller
authors.forename: Michelle
authors.initials: M
authors.lastname: Ly
authors.forename: Alastair
authors.initials: A
authors.lastname: Kyle
authors.forename: Saeid
authors.initials: S
authors.lastname: Golbidi
authors.forename: Yingjin
authors.initials: Y
authors.lastname: Wang
authors.forename: Keith
authors.initials: K
authors.lastname: Walley
authors.forename: Andrew
authors.initials: A
authors.lastname: Minchinton
authors.forename: Ismail
authors.initials: I
authors.lastname: Laher
authors.forename: Aly
authors.initials: A
authors.lastname: Karsan
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003097:Collateral Circulation; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D005263:Femoral Artery / Q000601:surgery; D006614:Hindlimb; D007511:Ischemia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008026:Ligation; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000098:blood supply*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D051880:Receptors, Notch / Q000378:metabolism*; D012039:Regional Blood Flow; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014664:Vasodilation; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D051880:Receptors, Notch; D014157:Transcription Factors; D000098662:Vasodilator-Stimulated Phosphoprotein; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse