Notch-Dependent Regulation of the Ischemic Vasodilatory Response—Brief Report

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 33; no. 3; pp. 510 - 512
• Main Authors: Chang, Alex C.Y, Patenaude, Alexandre, Lu, Katherine, Fuller, Megan, Ly, Michelle, Kyle, Alastair, Golbidi, Saeid, Wang, Yingjin, Walley, Keith, Minchinton, Andrew, Laher, Ismail, Karsan, Aly
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.03.2013
• Subjects: Animals; Cell Adhesion Molecules - metabolism; Collateral Circulation; Disease Models, Animal; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiopathology; Femoral Artery - surgery; Hindlimb; Ischemia - genetics; Ischemia - metabolism; Ischemia - physiopathology; Laser-Doppler Flowmetry; Ligation; Mice; Mice, Transgenic; Microfilament Proteins - metabolism; Muscle, Skeletal - blood supply; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type III - metabolism; Phosphoproteins - metabolism; Phosphorylation; Receptors, Notch - metabolism; Regional Blood Flow; Signal Transduction; Transcription Factors - genetics; Transcription Factors - metabolism; Tyrosine - analogs & derivatives; Tyrosine - metabolism; Vasodilation
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/ATVBAHA.112.300840

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. METHODS AND 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. CONCLUSION—Endothelial Notch activation is required for NO production and reactive vasodilation in a femoral artery ligation model.