Grant: Doctoral: Vanier Canada Graduate Scholarships

Heart disease is the leading cause of death worldwide. Atherosclerosis, the underlying cause of heart disease, is characterized by an accumulation of fat within the arteries that supply blood to the heart, narrowing these blood vessels and impairing blood flow. The accumulation of fat within artery walls, called 'plaque', is also associated with the buildup of different cell types filled with fat called 'foam cells'. Over time, the plaques grow and can become vulnerable to rupture, creating a blood clot which obstructs the blood vessels and leads to a heart attack or stroke. A major risk factor for atherosclerosis is high levels of circulating blood cholesterol. Current therapies to treat atherosclerosis consist of cholesterol-lowering therapies which prevent the progression of plaques, but these therapies do not cure the disease nor drive plaque shrinking. Discovery of drugs which could reduce plaque size and reverse atherosclerosis would prove to be a breakthrough. All the cells in our bodies possess an intrinsic ability to degrade defective or excess of cellular components through a recycling system named autophagy. This process is key to maintaining balance in cells. During heart disease development, autophagy becomes dysfunctional. Autophagy can mediate fat degradation and export excess fat out of foam cells for excretion through the feces. Our project aims to investigate the mechanism of fat degradation through autophagy for plaque shrinkage and the enhancement fat degradation via autophagy to promote plaque size reduction. For these studies, we will engineer a mouse that will allow us to track autophagy in real time and a small compound that can selectively enhance the degradation of fat through autophagy. Gaining a better understanding of the role of autophagy in foam cells may identify new therapeutic intervention and new targets to shrink atherosclerotic plaques, bypassing the need for lifelong therapies or invasive surgical procedures.