Ischemia is not required for arteriogenesis in zebrafish embryos

Gray, Caroline, Packham, Ian M., Wurmser, François, Eastley, Nicholas C., Hellewell, Paul G., Ingham, Philip W., Crossman, David C. and Chico, Timothy J. A. (2007) Ischemia is not required for arteriogenesis in zebrafish embryos. Arteriosclerosis, Thrombosis, and Vascular Biology, 27 (10). pp. 2135-2141. ISSN 1079-5642

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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 HIF1α 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. We developed a model of arteriogenesis using the zebrafish embryo, and we show that these develop collateral vessels in response to arterial occlusion in a nitric oxide– and myeloid cell–dependent manner. This occurs in the absence of hypoxia, implying that ischemia is not required for arteriogenesis.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Norwich Clinical Trials Unit
Depositing User: Rhiannon Harvey
Date Deposited: 18 May 2011 08:03
Last Modified: 09 Jan 2024 01:22
DOI: 10.1161/ATVBAHA.107.143990

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