Platelet free radical signalling in type II Diabetes Mellitus : effect of fish oil supplementation

• Main Author: McConville, Maeve
• Published: Queen's University Belfast 2008
• Subjects: 612.3
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.492027

Chapter 1 introduces the pathological changes that occur in the endothelium during diabetes mellitus (OM). Sources of nitric oxide, superoxide and the enzymes responsible for free radical production are defined within the vascular system in health and dysfunction. Therapeutic properties of omega-3 PUFA are discussed and the implications for cardiovascular disease. The aim of this thesis was to shed more light on the role of caveolin-1 in pathogenesis of OM II by using a well established platelet model for vascular endothelium. Also to evaluate the impact of omega-3 fatty acids derived from fish oil on platelet reactivity, with particular attention to nitric oxide synthase III and NAO(P)H oxidase systems in patients with OM. Chapter 2 introduces the platelets as an in vivo model of endothelium. Studies confirmed the presence of NOS III and regulatory proteins in the platelet. Identification of caveolin-1 is reported in platelets localised to the membrane despite lack of . caveolae. Chapter 3 assessed the effect of omega-3 PUFA on nitric oxide, superoxide and nitrite, an indicator of nitric oxide production detected in platelets. Investigation into caveolin-1 splice variant mRNA expression and efforts to unravel the pathogenic molecular mechanisms responsible for the changes observed was described. Chapter 4 NAOPH oxidase was confirmed as prevalent source of reactive oxygen species in OM II. NAOPH oxidase cytosolic subunits expression and localisation of p47phox and Rac1 were investigated in OM II platelets post fish oil treatment. Enhanced localisation of subunits to membrane lipid rafts was observed in OM II. Omega-3 PUFA supplementation induced compartmentalisation of subunits. partially explaining decreased NAOPH oxidase activity. Chapter 5 Investigation into platelet reactivity and potential to aggregate following n-3 PUFA addition. Chapter 6 Present the final discussions. Chapter 7 Bibliography.