The evolving role of high density lipoprotein function in cardiovascular risk and its modualtion by dietary antioxidants

The link between HDL and cardiovascular disease (CVD) is substantially more complex than ) originally thought. Until recently, the concentration of HDL was deemed sufficient in predicting future cardiovascular events. However, HDL function can become compromised in various disease states, resulting in reduced cardio-protection and the production of dysfunctional HDL with reduced anti-atherogenic properties. Antioxidants have been implicated in ameliorating the damaging oxidative processes associated with dysfunctional HDL and atherosclerosis. Therefore, this thesis focuses on the evolving role of HDL function and had three main aims: i) to assess the complex relationship between HDL-cholesterol concentration and HDL function, ii) to assess the modulation of HDL function by the ) predominant form of vitamin E, α-tocopherol, encompassing in vitro and ex vivo investigations and iii) to assess the modulation of HDL function by lycopene by dietary interventions. Various HDL-associated enzymes, including SAA, PON-I, CETP and LCAT, indicative of HDL function, were measured in serum and in HDL2&3 by a combination of ELISA., spectrophotometric and fluorometric assays. The main findings demonstrated that HDL-cholesterol concentration was modestly predictive of serum aspects of HDL function, however, this was enhanced upon analysis of the HDL subfractions, distinctly regarding PON-I and CETP activity, which were particularly efficient in predicting HDL function. This may be of particular use to the pharmaceutical industry for the manufacture of drugs which specifically target these enzymes. Furthermore, it has also provided evidence for the cautious use of antioxidant vitamins in improving HDL function, as indicated by: i) a detrimental decrease in HDL function by α-tocopherol supplementation in a normal weight population and ii) a beneficial increase in HDL function attributed to lycopene in an overweight population. Therapeutic normalisation of attenuated anti-atherogenic HDL function in terms of both quantity and quality of HDL particles is the target of innovative pharmacological approaches to raising HDL.EThOS - Electronic Theses Online ServiceGBUnited Kingdo