Grant: Master's Award: Canada Graduate Scholarships

Abdominal aortic aneurysm (AAA) is a leading cause of mortality in North America. It is especially prevalent in males between 55 to 80 years old. AAA is a chronic inflammatory cardiovascular disorder characterized by a minimum of 1.5 fold increase in the diameter of the abdominal aorta, especially in the infrarenal segment in humans. Its distinct morphological characteristics include the breakdown of extracellular matrix, smooth muscle cell programmed death and infiltration of inflammatory cells into the outer layer of the aortic wall. Chronic inflammation occurs throughout the thickness of the vessel wall, contributing to its morphological changes. Eicosanoid inflammatory mediators, namely prostaglandins and leukotrienes, are involved in the disease mechanisms in aneurysm development and progression. Much research has been conducted with the aim of elucidating the roles of each class of eicosanoids in aneurysm development. Understanding the molecular mechanisms by which eicosanoids contribute to AAA provides the necessary theoretical knowledge for disease diagnosis, prognosis and to reduce mortality rates. Past researchers have focused on detecting altered concentrations of specific mediators of the two pathways in comparison to non-AAA animal models or human cell cultures. In the present study, the level of gene expression of the crucial enzymes (ALOX5, ALOX5AP, PTGS1, PTGS2, PTGES, and PTGER4) in the prostaglandin and leukotriene pathways will be measured in human AAA tissues. Our use of human tissues will eliminate confounding factors associated with the use of exogenous stimuli for AAA development in animal models and go beyond the limitations of cell cultures. The possibility of interactions of lipid mediators within and between the two pathways may be examined, as these may play a role in AAA progression. To our knowledge, this is the first study to examine the role of both these major eicosanoid pathways in human AAA tissues.