Grant: Project Grant

Heart attacks and strokes are caused by a buildup of fats, including cholesterol, as well as inflammation in arteries. This buildup is known as atherosclerosis. These diseases are the leading cause of death and decreased quality of life in Canada and worldwide, as well as an enormous economic burden on the healthcare system. Until now it was assumed that most of the cholesterol that builds up in coronary and other arteries occurs in a type of white blood cell called macrophages. However, recently while studying human hearts donated by people having a heart transplant, we discovered that the majority of cells that accumulate excess cholesterol in human coronary arteries are actually smooth muscle cells. These cells were already known to be the main cell type in the 'plaques' that build up in arteries, but their importance as the main place cholesterol deposits had never been recognized until now. This information provides a whole new way of looking at how atherosclerosis develops, and how to design new treatments to reduce the death-toll and poor quality of life it causes. The goals of this research are to understand: 1) the exact contribution of smooth muscle cells to total cholesterol overload in plaques; 2) whether mouse models used to study atherosclerosis have the same buildup of cholesterol in smooth muscle cells as humans and are therefore good models to study this problem; 3) what the reasons are for the loss of a key cholesterol exporter that we also discovered in the plaque smooth muscle cells; and 4) how to overcome this cholesterol accumulation problem in these cells, either by increasing this exporter or by bypassing it to get the cholesterol out of the cells. Our recent findings are groundbreaking, and the results of this further research stand to revolutionize how we prevent heart disease and stroke, for the benefit of Canadians and people worldwide.