Grant: Doctoral: Vanier Canada Graduate Scholarships

Atherosclerosis is the main cause of heart disease - the leading cause of death in Canada. It is characterized by the buildup of fatty deposits, called plaques, on the inside walls of arteries. As plaque builds up, the artery gradually narrows and can become clogged, causing a heart attack or stroke. Macrophages, cells of our immune system, ingest modified lipid components of the plaques. By taking up massive amounts of lipids, these macrophages become 'foam cells'. Reversal of cholesterol accumulation in macrophages has been shown to atheroprotective, drawing interest to compounds that remove excess cholesterol from macrophages as potential therapeutic agents for the treatment of atherosclerosis. Researchers have shown that oxysterols, biological compounds related to cholesterol, do enhance cholesterol efflux from macrophages and prevent foam cell formation. However, the impact of oxysterols in foam cells, the diseased macrophages in atherosclerotic plaques, is unknown. Whether oxysterols can promote cholesterol efflux in macrophage foam cells and reverse lipid accumulation in these cells is the focus of my research project. So far, my studies have shown that two different oxysterols have opposite effects on cholesterol efflux. While one increased efflux from foam cells, the other promoted cholesterol accumulation and impaired cholesterol efflux. It is essential to understand what characteristics makes one oxysterol versus another better able to increase cholesterol efflux in macrophage foam cells. This research will provide information as to which oxysterol can be considered for the treatment of atherosclerosis, and what features are desirable for potential compounds designed for the pharmacological treatment of atherosclerosis. Treatment of atherosclerosis would greatly lower the risk of developing cardiovascular complications, and would thus translate to improved Canadian health.