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Title: Mechanisms of glucocorticoid-mediated inhibition of angiogenesis
Author: Logie, James John
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
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The work in this thesis explores the hypothesis that glucocorticoid-mediated inhibition of angiogenesis is the result of direct modulation of growth factor signalling within the vascular endothelial cells. A well-characterised 2-dimensional in vitro model of human endothelial tube formation was introduced. Glucocorticoids were shown to inhibit tube formation in this model via stimulation of glucocorticoid receptors and this process was not influenced by intra-cellular glucocorticoid metabolism by 11β-hydroxysteroid dehydrogenases. This demonstration that glucocorticoids inhibit angiogenesis by acting directly on the endothelium is consistent with, and extends observations of glucocorticoid-mediated angiostasis in rodent aortic rings and during cutaneous wound healing. Molecular and biochemical assays suggested that glucocorticoids inhibit tube formation by altering the balance of pro and anti-angiogenic factor activity. Time-lapse imaging of tube formation, combined with assays of endothelial cell migration and proliferation, indicated that glucocorticoids reduce tube formation, rather than accelerating degradation of existing tubes, by preventing morphological changes in the cells but do not inhibit cell division or migration. In conclusion, these studies demonstrate that glucocorticoids can inhibit angiogenesis by directly inhibiting morphological changes required for tube formation by endothelial cells but without altering migration or proliferation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available