Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.748850
Title: A study of the effects of iron deficiency on cardiac function
Author: Chung, Yu Jin
ISNI:       0000 0004 7232 5365
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2017
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Abstract:
The research presented in this thesis is an interdisciplinary study of the effects of iron deficiency on cardiac physiology. The aim of the study was to gain insight into the mechanism by which cardiac function is affected by iron deficiency, induced through the administration of an iron-deficient diet, on a murine model. Chapter 3 of this thesis introduces the mouse model, demonstrating that the administration of an iron-deficient diet does lead to iron deficiency, and in some animals, anaemia. It also provides in vivo evidence of impairment of heart function in iron-deficient animals. Alterations in cardiac function could be rescued by correction of the iron deficiency by intravenous iron supplementation. Chapter 4 describes the study which investigated the effects of iron deficiency on the cardiac gene expression profile using RNA-sequencing technology. This study revealed that the administration of an iron-deficient diet leads to many genome-wide changes, some of which are likely to be related to the cell's stress response. Chapter 5 presents the study into cardiac metabolism. Iron-deficient hearts were found to have increased glycolytic flux and lactate production. Alterations in metabolism occurred in the absence of changes in mitochondrial numbers or morphology. Instead, the proposed mechanism for changes in cardiac energetics is hypoxia of the cardiac tissue. Chapter 6 reports the findings of the study which explored the effects of an iron-deficient diet on the cardiac calcium signaling pathway. Iron deficiency was associated with higher diastolic calcium levels and decreased calcium transient amplitude, which could be prevented by reversal of iron deficiency by intravenous supplementation of iron. Overall, this thesis provides evidence that severe iron-deficiency anaemia is sufficient to cause modest impairment of cardiac function and that this functional impairment is the result of complex alterations that occur at the genetic, metabolic and signaling level.
Supervisor: Swietach, Pawel ; Robbins, Peter A. Sponsor: Vifor Pharma
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.748850  DOI: Not available
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