Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.662041
Title: Glucocorticoids and angiogenesis
Author: Small, G. R.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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Abstract:
It was hypothesised that generation of endogenous glucocorticoids by 11βHSD1 within the vessel wall regulates angiogenesis. In vitro mouse aortic ring cultures established that physiologically-relevant concentrations of glucocorticoids inhibit angiogenesis in a glucocorticoid receptor-dependent manner.  In addition 11βHSD1 was found to modulate glucocorticoid-induced angiostasis, for 11dehydrocorticosterone (a substrate for 11βHSD1) although angiostatic in C57B16 aortae did not inhibit angiogenesis in llβHSD1 deficient animals. In vivo using subcutaneous sponge implants in mice, endogenous glucocorticoids were found to inhibit angiogenesis: sponges in adrenalectomised mice grew more vessels compared to sponges from sham-operated animals. 11βHSD1 regulated the angiostatic effects of glucocorticoids, for cortisone (the human equivalent of 11dehydrocorticosterone), although angiostatic in controls did not inhibit angiogenesis in 11βHSD1 deficient mice. In pathology in cutaneous wounds and infracted myocardium endogenous glucocorticoids were found to inhibit angiogenesis. RU38486, (a glucocorticoids receptor antagonist) in comparison to placebo enhanced angiogenesis in both tissues. In similar studies in C57B16 or llβHSD1 deficient mice, 11βHSD1 was found to tonically repress angiogenesis and impair left ventricular remodelling post infarction. Thus 11βHSD1 deficient mice had increased myocardial revascularisation and preserved left ventricular function. In conclusion, by using in vitro, in vivo, and pathological models, endogenous glucocorticoids were seen to inhibit angiogenesis. In addition, 11βHSD1 regeneration of glucocorticoids tonically repressed angiogenesis and influenced left ventricular remodelling post myocardial infarction. Thus 11βHSD1 appears to be an attractive therapeutic target for the management of tissue revascularisation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.662041  DOI: Not available
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