Grant: Operating Grant

In the last few decades, it has been recognized that the lining cells of the blood vessels, the endothelial cells, play a major protective role in health and disease. When not functioning properly, disease occurs, and this is most commonly manifest by atherosclerosis, heart attacks, angina, strokes, and blood clots in the legs and lungs, all of which continue to be major causes of disability and death. The mechanisms that protect the blood vessel endothelial cells from damage are complex and not fully understood. One well-characterized system prevents blood from abnormally clotting. Another prevents the immune system, the so-called complement system, from over-reacting and destroying any injured endothelial cells. It is not clear how these two mechanisms are co-ordinated. We have recently identified links between the two, but much more work is necessary to better understand the relationship. This new knowledge will lead to a clearer view as to why disease occurs, and will allow for the development of new therapies that enhance the protective activities of both, thereby preventing blood vessel disease. The overall goal of our studies is to understand how the blood clotting system interacts with the complement system, and how these two systems are co-ordinated to protect the blood vessel endothelial cells from damage that would lead to heart disease and stroke. We hope to determine how genetic abnormalities in some of the components of these systems increase the risk of disease, which will allow for the development of new and more effective therapies.