Grant: Project Grant

Atherosclerosis leads to heart attacks and strokes and is a leading cause of death in Canada. The first step in the disease is the build-up of the bad cholesterol, LDL, in the wall of blood vessels. Specifically, LDL builds up under the innermost layer of arteries, called the endothelium. How the LDL gets under the endothelium is very poorly understood. We have discovered ways to study this process, which is known as LDL transcytosis. In earlier work, we discovered two molecules on the cell surface that bring LDL into the endothelial cell but almost nothing is known about what happens next. We now wish to understand the route taken by LDL as it traverses the cell. Does it interact with other parts of the cell? How does it move through the crowded cell? Understanding how LDL navigates across the endothelial cell will help us develop ways to prevent the development of heart disease. If we can prevent cholesterol from accumulating in the blood vessel wall, we will prevent heart disease and stroke. We will use sophisticated microscopes to study the process by which cholesterol builds up under the special cells that line blood vessels, known as endothelium. We will identify the specific molecules that regulate this build-up. We will also prove that our findings from cells hold true in mice, which are the typical animals used in studies of atherosclerosis. We will compare our findings using cells from men as well as women to determine if there is a sex-based difference. We are the only lab in Canada to study this process of transcytosis, by which the bad cholesterol (LDL) gets under endothelial cells. We therefore have the potential to make huge advances in this field of research.