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Title: Glycosaminoglycans of the endothelial surface layer in type 1 diabetic nephropathy
Author: Russell, Amy
ISNI:       0000 0004 6056 8722
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2015
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Diabetes mellitus is a major worldwide health concern. Many diabetics not only suffer general ill health, but many will suffer from microangiopathies such as nephropathy- the main cause of end stage renal failure. One of the earliest clinical manifestations of diabetic nephropathy (DN) is proteinuria. Given that proteinuria reflects increased microvascular permeability, I sought to determine if removing constituents of a carbohydrate-rich layer on the luminal aspect of blood vessels, the endothelial glycocalyx, could mimic the increased permeability observed in diabetes. I wanted to determine if these alterations in permeability also manifested in a reduction in glycocalyx thickness and then to purify glomerular endothelial cells (GEnCs) and screen for alterations in glycocalyx-related genes in diabetes mellitus. Male Sprague-Dawley rats, which were hyperglycaemic 1 week post STZ injection, displayed significant increased glomerular water permeability (LpA/Vi) compared to sham-injected rats. Diabetic rats perfused with hyaluronidase displayed a significant reduction in LpA/Vi compared to diabetics alone. This was not associated with a reduction in glycocalyx volume, as measured using lectin staining. Genes related to the synthesis and degradation of glycosaminoglycans (GAGs) were not altered in STZ-injected mice 9 weeks following injection. Diabetes causes an increase in LpA/Vi, which appears to precede the development of proteinuria. This may provide a useful therapeutic target for clinical use. It appears that at this time point in this model, there was no associated reduction in glycocalyx depth. The genetic explanation for these changes remains to be elucidated.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available