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Title: Toxicity of oxidised LDL and its lipid components to human monocyte-macrophages
Author: Clare, K.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1999
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The aim of the work in the present study was to investigate the toxicity of oxidised LDL and its lipid components to human monocyte-macrophages, as these cells are more physiologically relevant than those used previously. The results showed that oxidised LDL was indeed toxic to human monocyte-macrophages. The cytotoxicity of oxidised LDL correlated well with its content of lipid oxidation products. Investigation of the effects of oxidising different lipid components of LDL showed that oxidation products of the polyunsaturated fatty acids of the phospholipid and cholesterol esters were cytotoxic. Oxidation of the cholesterol-containing components of LDL only occurred in the presence of polyunsaturated fatty acids. Oxidation of low concentrations of cholesterol resulted in the production of oxysterols at non-toxic concentrations, apparently at the expense of fatty acid oxidation, thus reducing the toxicity of the fatty acid oxidation products. Oxidation of higher concentrations of cholesterol resulted in the production of oxysterols at toxic concentrations. The findings of this study support the recent suggestions that saturated fatty acids should be replaced by monounsaturated rather than polyunsaturated fats, in order to minimise LDL oxidation and toxicity. It has been suggested that apoptosis may be involved in foam cell death in the lesion, and oxidised LDL has also been shown to induce this type of cell death in various cells, including monocyte-macrophages. Oxidation products of cholesterol were shown to induce apoptosis in human monocyte-macrophages, suggesting that it may be these components of oxidised LDL which lead to apoptotic cell death in the lesion. Further work should determine whether oxidation products of fatty acids also have this effect. The finding that components of oxidised LDL may be responsible for the foam cell death leading to the formation of the lipid core suggests further mechanisms of intervention. It may be possible to encourage macrophage uptake of LDL while maintaining the ability of lipid-loaded cells to leave the arterial wall.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available