Grant: Operating Grant

The second leading cause of death in Canada is heart disease, most of it caused by atherosclerosis. In this disease process, there is build-up of cholesterol and other materials that alter the inner lining of arteries supplying blood to the heart, leading to blood clots, chronic inflammatory responses and heart attack. The inflammatory responses in atherosclerosis involve many types of immune cells such as monocytes, macrophages, T cells and dendritic cells (DCs). In contrast to numerous studies regarding the disease-promoting roles of macrophages and T cells, the roles of DCs in atherosclerosis are unclear. Our groups and others have uncovered DCs in the healthy and atherosclerotic blood vessels. Here, we hypothesize that vascular DC subsets will have differential effects on the course of atherosclerosis. In the present proposal, we will first characterize subsets of DCs in healthy and atherosclerotic blood vessels. Then, using genetically modified mice to selectively manipulate DC subsets, we will investigate their function in the context of atherosclerosis. DCs are now believed to orchestrate the interactions of more than a dozen type of immune system cells, and they also play a role in preventing the immune system from attacking the body's own tissues. Therefore, understanding the basic biology of dendritic cells and their subsets will lead to ways to harness them therapeutically in treating or preventing atherosclerosis.