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Title: Characteristics and protection of hearts and myocytes isolated from mice fed high-fat diet
Author: Hawi, Jihad
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2013
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Atherogenic high-fat diet has been used to accelerate atherosclerosis in apolipoprotein knock-out (apoE-/-) mouse. Hearts of male apoE-/- mice fed high-fat diet are ischaemic, show extensive coronary disease, suffer infarct and sudden death. This work is a further characterisation of this model with emphasis on female apoE-/-mice. In particular, the occurrence of atherosclerosis, calcium cycling, oxidative stress, the response to cardiac insults in the presence of cardioplegia and the role of pravastatin in reversing coronary disease. Mice (apoE-/- and wild-type) were fed either standard chow diet or atherogenic diet. After 24 weeks feeding, hearts were extracted and used for: Langendorff perfusion, isolation of myocytes, protein extraction and histology. A model of oxidative stress in isolated cardiomyocytes has been developed to compare vulnerability in relation to diet and gender. The effect of pravastatin on incidence of atherosclerosis in the coronary arteries of male apoE-/- as result of high-fat was studied. In comparison to male apoE-/-mice only a small number of hearts from female apoE-/- mice fed high-fat diet showed evidence of occlusive coronary disease. High-fat feeding significantly altered the characteristics of intracellular calcium transients as well as the expression of cardiac proteins involved in excitation-contraction coupling. Cardiomyocytes from apoE-/- mice fed highfat diet were more resistant to oxidative stress than myocytes from mice fed normal diet or from wild type mice . High-fat diet in male apoK/- mice tended to increase pro-apoptotic signalling and cardiac expression of mitochondrial uncoupling protein 3 compared to male fed normal diet or to female on highfat diet. Cardioplegia offers strong cardioprotection of apoE-/-mice irrespective of diet or gender. In conclusion, this work shows that development of coronary disease IS gender related and alters the characteristics of calcium cycling and the ability of cardiomyocytes to respond to oxidative stress. Pravastatin did not alter sudden death triggered by high-fat diet. However, it affected the lipid composition of the arterial lesions.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available