Heart attack, heart failure, and stroke are major causes of disability and death in BC and worldwide. The main cause of these conditions is the buildup of blockages or "plaque" in arteries in a process called atherosclerosis. For a long time, it was thought that the main place where fats (like cholesterol) build up in plaque are white blood cells called macrophages, but our laboratory made the novel discovery that it is actually smooth muscle cells (SMCs) in arteries that are most prone to becoming cholesterol-overloaded, which has important implications on developing ways to prevent heart attack and stroke.
We now propose to perform an in-depth characterization of SMCs to understand how they become overloaded with cholesterol. In addition, we will determine whether differences in SMC gene expression protect some people from plaque formation, how cholesterol-overloaded SMCs in human hearts respond to cholesterol-lowering medications, and whether turning on a particular gene in SMCs can prevent them from forming plaque and remove excess cholesterol from SMCs after it has been deposited. This work will provide vital new knowledge to reduce the burden of heart attack, stroke and heart failure in BC and beyond.