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Title: The protective role of high density lipoproteins in atherosclerosis
Author: McPherson, Peter Andrew Cameron
Awarding Body: Queen's University of Belfast
Current Institution: Queen's University Belfast
Date of Award: 2008
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Abstract:
Chapter 1 provides an overview of the structure, composition, metabolism and clinical significance of the plasma lipoproteins, and specifically focuses on high density lipoprotein (HDL), and its major subfractions (HDL2 and HDL3). Chapter 2 describes the development and validation of a rapid ultracentrifugation method for the isolation of HDL2 and HDL3. This facilitated the examination of HDL subfractions in a variety of contexts, and lead to the discovery of a novel pro-oxidant effect of HDL on the oxidation ofvery low density lipoprotein (VLDL). Chapter 3 explores the role which HDL subfractions may play in endothelial dysfunction, by examining their effect on human coronary artery endothelial cells. Overall, native HDLs reduced the expression of pro-inflammatory molecules; in the oxidised state, HDLs promoted the release ofpro-inflammatory molecules. Chapter 4 describes the involvement of lecithin:cholesterol acyltransferase in lipoprotein oxidation and atherosclerosis. This work identified a duplicitous effect of LCAT during oxidation ofApo B-containing lipoproteins; it acted as a pro-oxidant during VLDL oxidation, but as an antioxidant during oxidation oflow density lipoprotein (LDL). Chapter 5 reports the effect of metfonnin and pioglitazone on the composition and oxidation of HDLz and HDL3, in a group of obese and overweight men. Results demonstrated that pioglitazone exhibited a broader range of effects on HDL subfractions, particularly by increasing the HDLz-to-HDL3 ratio - a change associated with improved reverse cholesterol transport. Chapter 6 presented a clinical case study on inherited cholesterol ester transfer protein (CETP) deficiency. HDL isolated from the proband had an abnormal composition and oxidation profile. Moreover, HDLisolated from the proband had a reduced pro-oxidant effect towards VLDL, confinning the participation ofCETP in this novel reaction ofHDL. Chapter 7 provides a general discussion, and concluding remarks, for the main body of the thesis, including suggestions for future work.
Supervisor: Not available Sponsor: Not available
Qualification Name: Queen's University of Belfast, 2008 Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.492013  DOI: Not available
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