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Title: Identification of novel drivers of collateral vessel remodelling in the chick embryo
Author: Hoggar, Emily
ISNI:       0000 0004 5356 4950
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2014
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Arterial occlusion accounts for high rates of mortality in the western world. Strategies to bypass an occlusion by activating collateral vessels could reduce the consequences of arterial diseases. This thesis investigates the genes involved in collateral vessel remodelling in the chick embryo to gain insight into the process. Ligation of the right proximal vitelline artery of HH st 17 chick embryos occluded blood flow to the right hand side of the extra-embryonic tissue and vitelline vessel network. Collateral vessels were seen to develop from the pre-existing, left (unligated) vitelline artery and extended across the midline to carry arterial blood to the un-perfused side of the extra-embryonic tissue. The remodelling process was active over 48 hours and developed many small collateral vessels into a few, main conducting arteries. The number of collateral vessels peaked at 12 hours post tied-ligation and then decreased, whilst collateral vessel diameter continued to increase over the time period. Analysis of the global transcriptional profile of collateral vessels in the chick embryo was assessed following ligation, during early stages of collateral vessel development (4 hours), at the point of pruning and remodelling of the collateral network (12 hours). Collateral vessel formation in the chick embryo was found to be associated with a unique and specific gene expression profile. Phosphodiesterase 10A (PDE10A), an cAMP hydrolysing enzyme, was upregulated in tied-ligated embryos at 4 hours post tied-ligation and hypothesised to play a role in the remodelling process. To study PDE10A papaverine hydrochloride was used to inhibit the enzyme. Papaverine had no effect on normal vessel development but significantly impaired collateral vessel diameter from 6 hours post-ligation. This effect was rescued by co-treatment with Protein Kinase A inhibitor, Rp-8-Br-cAMPS. To begin an assessment of the role of PDE10A in collateral vessel remodelling, proliferation was investigated, in vivo. However, a mechanism of action for PDE10A has yet to be elucidated.
Supervisor: Chico, T. J. ; Placzek, M. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available