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ZIRC
ZFIN ID: ZDB-PUB-070806-19
Ischemia Is Not Required for Arteriogenesis in Zebrafish Embryos
Gray, C., Packham, I.M., Wurmser, F., Eastley, N.C., Hellewell, P.G., Ingham, P.W., Crossman, D.C., and Chico, T.J.
Date: 2007
Source: Arterioscler. Thromb. Vasc. Biol.   27(10): 2135-2141 (Journal)
Registered Authors: Chico, Tim J., Gray, Caroline, Ingham, Philip
Keywords: collateral circulation, angiogenesis, nitric oxide, blood flow, zebrafish
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Aortic Diseases/embryology
  • Aortic Diseases/genetics
  • Aortic Diseases/metabolism
  • Aortic Diseases/physiopathology*
  • Arterial Occlusive Diseases/embryology
  • Arterial Occlusive Diseases/genetics
  • Arterial Occlusive Diseases/metabolism
  • Arterial Occlusive Diseases/physiopathology*
  • Arteries/embryology
  • Arteries/growth & development*
  • Arteries/metabolism
  • Basic Helix-Loop-Helix Transcription Factors/genetics
  • Basic Helix-Loop-Helix Transcription Factors/metabolism
  • Cell Hypoxia
  • Collateral Circulation*
  • Disease Models, Animal
  • Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
  • Ischemia/embryology
  • Ischemia/genetics
  • Ischemia/metabolism
  • Ischemia/physiopathology*
  • Microscopy, Confocal
  • Mutation
  • Myeloid Cells/metabolism
  • Neovascularization, Physiologic*
  • Nitric Oxide/metabolism
  • Nitric Oxide Synthase/metabolism
  • Proto-Oncogene Protein c-fli-1/genetics
  • Proto-Oncogene Protein c-fli-1/metabolism
  • RNA, Messenger/metabolism
  • Time Factors
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 17656667 Full text @ Arterioscler. Thromb. Vasc. Biol.
FIGURES
ABSTRACT
OBJECTIVE: The role of ischemia in collateral vessel development (arteriogenesis) is a contentious issue that cannot be addressed using mammalian models. To investigate this, we developed models of arteriogenesis using the zebrafish embryo, which gains sufficient oxygenation via diffusion to prevent ischemia in response to arterial occlusion. METHODS AND RESULTS: We studied gridlock mutant embryos that suffer a permanently occluded aorta and show that these restore aortic blood flow by collateral vessels. We phenocopied gridlock mutants by laser-induced proximal aortic occlusion in transgenic Fli1:eGFP/GATA1:dsRED embryos. Serial imaging showed these restore aortic blood flow via collateral vessels by recruitment of preexisting endothelium in a manner similar to gridlocks. Collateral aortic blood flow in gridlock mutants was dependent on both nitric oxide and myeloid cells. Confocal microscopy of transgenic gridlock/Fli1:eGFP mutants demonstrated no aberrant angiogenic response to the aortic occlusion. qPCR of HIF1alpha expression confirmed the absence of hypoxia in this model system. CONCLUSIONS: We conclude that NO and myeloid cell-dependent collateral vessel development is an evolutionarily ancient response to arterial occlusion and is able to proceed in the absence of ischemia.
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