Grant: Project Grant

Heart attacks and strokes are a major cause of death and disability in Canada and around the world. It is known that a condition called atherosclerosis (the thickening of the blood vessel walls) is the underlying cause of most heart attacks and strokes. It is also known that certain risk factors, including smoking, obesity, high blood cholesterol, diabetes, and high blood pressure, promote the development of atherosclerosis. However, it is not known how or why this occurs. If we know how risk factors cause atherosclerosis, we can design ways to slow, stop or reverse disease progression. We have found a new pathway that might be an important link between cardiovascular risk factors and atherosclerosis. The objective of this study is to determine the role of this pathway in disease development and progression. The pathway that we have found involves a particular kind of stress (called ER stress). We believe that, when this stress is present, a factor (a protein) called GSK3 is activated. We have evidence that activated GSK3 can turn on other factors that can lead to the development of atherosclerosis. We have established a unique collection of cells and animal model systems that will allow us to investigate the links between risk factors - like diabetes - and the development of atherosclerosis. We are working in a step by step fashion to determine how risk factors cause ER stress, how ER stress activates GSK3 and how GSK3 is involved in atherosclerosis. In the course of these studies we hope to find ways in which this whole process can be blocked and perhaps reversed. In this way, our research could lead to the development of new effective treatments for cardiovascular disease.