Mechanisms of glucocorticoid-mediated inhibition of angiogenesis
dc.contributor.author
Logie, James John
en
dc.date.accessioned
2018-05-22T12:44:02Z
dc.date.available
2018-05-22T12:44:02Z
dc.date.issued
2008
dc.description.abstract
en
dc.description.abstract
Angiogenesis, the formation of new blood vessels from pre-existing vascular beds, is
a
requirement of embryonic development but only occurs in a limited number of
discrete processes in the healthy adult. In contrast, abnormal angiogenesis is central
to many pathological processes including: tumour growth, diabetic retinopathy and
arthritis. Consequently, pharmacological manipulation of angiogenesis has great
clinical potential.
en
dc.description.abstract
Angiogenesis is inhibited by glucocorticoids and this is exploited clinically for the
treatment of proliferating capillary haemangiomas in children. Despite this, the exact
mechanism(s) through which glucocorticoids inhibit angiogenesis is (are) unknown.
Whilst glucocorticoids can act directly on the vessel wall their effects on individual
cell types and on molecular signalling remain unclear. 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.
en
dc.description.abstract
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 ll(3-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.
en
dc.description.abstract
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.
en
dc.identifier.uri
http://hdl.handle.net/1842/30396
dc.publisher
The University of Edinburgh
en
dc.relation.ispartof
Annexe Thesis Digitisation Project 2018 Block 19
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dc.relation.isreferencedby
Already catalogued
en
dc.title
Mechanisms of glucocorticoid-mediated inhibition of angiogenesis
en
dc.type
Thesis or Dissertation
en
dc.type.qualificationlevel
Doctoral
en
dc.type.qualificationname
PhD Doctor of Philosophy
en
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