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Title: Lipoproteins, apoprotein A-1 containing particles and the development of atherosclerosis
Author: Vallance, David Thomas
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1993
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This study concerns the measurement and composition of high density lipoprotein (HDL) and mechanisms through which HDL might exert the proposed protective effect against coronary heart disease (CHD). The composition of HDL, particularly in respect of particles containing apoA-I but not apoA-II (LpAI) was studied after precipitation of apoB-containing lipoproteins. Differences in HDL cholesterol, apoA-I and LpAI between commonly used methods were modest and those differences were not due to selective precipitation of LpAI. All precipitation methods were equally effective at precipitating Lp(a). Families with a history of premature CHD but without perceived risk factors showed an enhanced expression of two established risk associations - hypercholesterolaemia and/or reduced levels of HDL. LpAI concentrations were reduced in males with premature CHD and LpAI was marginally superior to apoA-I and HDL cholesterol in correctly discriminating between those with CHD and those without. Moderate exercise, sufficient to increase HDL cholesterol, could potentially reduce CHD risk. However twelve months of moderate exercise in previously sedentary, middle-aged men did not produce any significant changes in serum lipids or apolipoproteins suggesting that the potential for modifying lipoprotein profiles in men using low intensity exercise is modest. Exercise might produce changes in lipoprotein concentrations by modifying lipoprotein lipase (LPL) and hepatic lipase (HL) activity. In individuals with low and high HDL cholesterol, apoA-I and HDL cholesterol concentrations were correlated with post heparin plasma LPL and inversely correlated with HL. Furthermore HL, but not LPL, activities were inversely correlated with LpAI concentrations in both groups. The mechanisms by which HDL may protect against atherosclerosis are unclear. However the data reported here on the discriminating power of LpAI particles, the failure of exercise to influence LpAI particle concentrations and the factors which may influence LpAI concentrations in plasma, indicate that further work will be required before LpAI can truly be described as the anti-atherogenic fraction of HDL.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available