Grant: CIHR New Investigator

Atherosclerosis leads to cardiovascular disease, the leading cause of death and morbidity in Canada. More than 50,000 strokes and 75,000 heart attacks occur in Canada every year, causing at least one in three deaths annually. Current therapeutic strategies to prevent atherosclerosis are primarily based on the use of lipid-lowering drugs, statins, which decrease concentrations of low density lipoprotein (LDL) cholesterol (sometimes referred as the 'bad' cholesterol) in the blood. The treatment of patients with statins reduces cardiovascular events by about 20 to 40%. Moreover, mounting evidence shows that lowering LDL cholesterol might not be enough for people at high risk of heart disease. Thus, there is an important and urgent need for new therapies. Numerous studies have provided unquestionable evidence that plasma levels of HDL cholesterol, sometimes referred as the 'good' cholesterol, are positively associated with protection against atherosclerosis. One of the most important roles of HDL in protection against atherosclerosis is the removal of cholesterol from macrophages. The initial and rate-limited step in this biological process is the removal of cholesterol from cells.Two proteins that play an important role in this step are the so-called ATP-binding cassette (ABC) transporters, ABCA1 and ABCG1. We are investigating how these proteins help macrophages get rid of excessive cholesterol. We will conduct the research using a broad range of cutting edge techniques in biochemistry, cell biology and molecular biology. Outcomes of our studies will provide fundamental information for the future design of new therapies to reduce the rates and severity of atherosclerosis, thereby benefiting millions of Canadians.