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The molecular mechanisms of diabetes mediated impaired wound healing and the development of therapeutic strategies.

Gadad, Pramod C.

Authors

Pramod C. Gadad



Contributors

Rachel M. Knott
Supervisor

Kerr H. Matthews
Supervisor

Abstract

Increased levels of blood glucose are associated with the vascular complications of diabetes. Microvascular complications lead to delayed wound healing in patients suffering from diabetes. Hypoxia and hyperglycaemia characterise a wound environment of a person with diabetes. Angiogenesis is central to restore the supply of oxygen and nutrients to the wounded tissue. Endothelial cell migration is central to angiogenesis which is aided by hypoxia and attenuated by hyperglycaemia. However, the molecular mechanisms underlying the disruption to angiogenesis of diabetic wounds are not completely understood. The effect of hypoxia and/or high glucose concentration on the endothelial cell migration in vitro was studied and an anti-oxidant, silymarin formulated as freeze dried wafer discs was tested for its beneficial effect. A radial migration and a wound healing assay were developed, validated and used to assess the effect of hypoxia and/or high glucose concentration on the migration of human endothelial cells of dermal origin. Circular and semi-circular monolayers of endothelial cells were used for the measurement of the migration by radial migration and wound healing assay respectively. Net migration was calculated by subtracting the radii at a specified time point from that measured at time zero. The migration was studied under normal (20%) or below (5%) normal oxygen tension in combination with normal (5mM) or high (20mM) glucose concentration. Endothelial cells were treated with an anti-proliferative agent, intracellular signal inhibitors and silymarin. Results demonstrated that hypoxia and high glucose concentration have opposing effects of increase (p

Thesis Type Thesis
Institution Citation GADAD, P.C. 2011. The molecular mechanisms of diabetes mediated impaired wound healing and the development of therapeutic strategies. Robert Gordon University, PhD thesis.

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GADAD 2011 Molecular mechanisms of diabetes (8.8 Mb)
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Copyright Statement
Copyright: the author and Robert Gordon University




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