Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.582727
Title: The effects of zinc deficiency on vascular smooth muscle cell function
Author: Allen-Redpath, Keith
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2013
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Abstract:
Dietary zinc deficiency affects one third of the world’s population and has more recently been associated with the development of atherosclerosis, however, its role in vascular smooth muscle cell (VSMC) function remains uncharacterised. VSMC’s are necessary for maintaining atherosclerotic plaque stability and any complications in VSMC function could have serious implications in vascular disease. The main aim of this study was to utilise in vivo and in vitro models of zinc deficiency to ascertain the effects this has on VSMC signalling processes. Rats were maintained on 2 and 6 weeks marginally zinc deficient diets which induced lower serum zinc concentrations. Carotid and aortic arterial tissue samples dissected from zinc deficient rats had significantly higher levels of VSMC apoptosis compared to those maintained on a zinc adequate diet. This occurred in parallel with increased dephosphorylation of the Bcl-2 associated death promoter (BAD) and attenuation of the pro-survival ERK1/2 pathway which maintains BAD in an inactive phosphorylated state. Two further mechanisms were further elucidated in vitro. Primary rat aortic smooth muscle cells (PRASMC) were incubated with plasma from zinc deficient rats and resulted in increased apoptosis and an overexpression of BAD similar to in vivo observations. However, this also occurred via sustained increases in [Ca2+]i leading to the activation of the BAD phosphatase calcineurin (which promotes activation of BAD via dephosphorylation) and increased oxidative stress. Further results have demonstrated that plasma from zinc deficient rats inhibits VSMC migration via decreased activity of osteopontin (OPN) an integrin receptor ligand and reduced activation of CREB. In addition, VSMC proliferation and differentiation in zinc deficiency was also assessed but no significant change was detected. Furthermore, these results were not due to a direct effect of zinc deficient environment rather secondary mechanisms in vivo via mediators released into the plasma. Taken together these findings demonstrate that marginally zinc deficient diets can induce VSMC apoptosis and decreased migration which may influence cardiovascular diseases such as atherosclerosis by inducing plaque vulnerability and further vascular complications.
Supervisor: Not available Sponsor: National Research Foundation of Korea ; University of Aberdeen
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.582727  DOI: Not available
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