The work carried out for this thesis examined the cardiovascular and antiinflammatory benefits of long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs). LC n-3 PUFAs have blood pressure lowering, anti-inflammatory and antithrombotic effects, however their exact mechanisms of action are still unclear. This project aimed to elucidate these mechanisms, by using a human cell culture model of vascular inflammation, and through dietary supplementation of people with mild, chronic vascular inflammation with capsules containing LC n-3 PUFAs. Vascular function was examined by dietary supplementation of a mouse model of chronic inflammation with LC n-3 PUFAs. The pro-coagulant glycoprotein von Willebrand factor (vWF) was of particular interest as excessive release of vWF from the endothelium is linked to endothelial dysfunction that might contribute to the manifestation of clinical complications associated with cardiovascular disease. The main findings of these studies were that: 1) LC n-3 PUFAs modulated the release of vWF in some phorbol ester-stimulated human umbilical vein endothelial cells by preventing actin cytoskeleton rearrangement. 2) Dietary supplementation of mildly hypertensive subjects with LC n-3 PUFAs increased incorporation of LC n-3 PUFAs into cell membrane phospholipids, without altering plasma vWF profile. 3) Dietary supplementation of a mouse model of abdominal aortic aneurysm with LC n-3 PUFAs prevented an increase in arterial blood pressure without affecting vascular reactivity. Collectively these findings highlight a novel mechanism of action of the LC n-3 PUFAs and suggest them as a potential adjunct treatment option for vascular inflammatory disease.
Submitted in the fulfilment of the requirements of the degree of Doctor of Philosophy, University of the Sunshine Coast, 2015.