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Title: Endothelial calcium-permeable TRP channels in vascular function and disease
Author: Hanrahan, Samuel Robert
ISNI:       0000 0004 5372 6534
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2015
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The transient receptor potential (TRP) Ca2+ permeable cation channels enable cells to respond directly to a variety of changes in their local environment. There is a growing body of evidence implicating TRPs in a variety of diseases, including endothelial dysfunction and cardiovascular disease. However, the expression profile and functional roles of TRPs in the human vasculature remain poorly characterised. This thesis was split into two main chapters to investigate expression and function of two separate TRP channels in endothelial cells. The first part concentrated on the evidence for a functional role for TRPM8 in endothelial cells and the second part investigated changes in expression and functional roles of TRPV4 in endothelial cells in hyperglycaemic conditions and in diabetic blood vessels from streptozotocin (STZ) injected rats. Patch-clamp, Ca2 + imaging and cell growth ass;3ys revealed functional expression and an important role for TRPM8 in endothelial physiology; immunocytochemistry and Western blot also confirmed plasma membrane and perinuclear bound TRPM8 protein expression ih these cells. However conventional PCR and qRT-PCR were unable to confirm TRPM8 mRNA expression. Hyperglycaemia in human aortic endothelial cells (HAoEC) lead to down-regulation of TRPV4 mRNA which was also seen in whole aorta, mesenteric artery, renal artery and retinal arterioles from STZ injected diabetic rats, as examined by qRT-PCR. Ca2+ Microfluorimetry studies revealed that TRPV4 mediated Ca2+ entry was down-regulated in HAoEC after 72 hour exposure to high D-glucose. Further work is required to elucidate the functional expression of TRP channels in the vasculature and to determine their role in the pathogenesis of endothelial dysfunction and associated cardiovascular disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available