Grant: CIHR Fellowship

Atherosclerosis is responsible for more deaths in Canada than any other disease. This illness is described as a chronic condition that is characterized by cholesterol build-up inside the arteries, called plaques. However, cholesterol can be transported outside the cells (efflux) of the atherosclerotic plaque, which can be beneficial for the cells. There is a protein in the body called apolipoprotein A-I (apoA-I) that accepts this cholesterol from the cells and forms particles of the "good" cholesterol (HDL) in the blood that protects against atherosclerosis. Adiponectin, a protein secreted by fat tissue, has beneficial effects by preventing formation of plaques in the arteries. Studies have shown that adiponectin is strongly associated with the level of the HDL in the blood. However, it is not known if adiponectin can directly increase "good" cholesterol production and function, which would be very beneficial against atherosclerosis. Our preliminary evidence showed that adiponectin can interact with apoA-I and stimulate cholesterol efflux efficiently in a human cell model of macrophages. My project will focus on the study of the interaction between adiponectin and apoA-I. I will perform several advanced laboratory experiments to assess if this interaction increases the production HDL and its "good" cholesterol function. In other words, I will determine if and in which manner adiponectin can enhance the ability of apoA-I to accept cellular cholesterol and generate HDL particles. I will also study their interaction by examining where exactly adiponectin binds on apoA-I. Overall, these findings may support the therapeutic potential of combining adiponectin and apoA-I, to increase HDL, the" good" cholesterol. These may prove to be significant discoveries to reduce atherosclerosis and its related diseases, such as stroke and heart attacks, and save lives!