Connective Tissue Growth Factor and fibrocyte recruitment to the myocardium

Heart disease is considered to be the number one killer of Canadians. An important part of many heart diseases is a process of heart scarring also called fibrosis that occurs in response to injury. Unfortuntely, while this process is benneficial initialy it can lead to replacement of heart muscle and worsening heart function. This means that when fibrosis occurs it can result in difficulty for the heart to pump blood into the body, a condition that is called heart failure and is associated with a high mortality rate. The mechanisms that results in fibrosis are not well characterized. Our laboratory is interested in studying the mechanisms that lead to heart muscle fibrosis, including why and how particular cells are attracted to the heart and participate in this process. In the present project we will study the role of a specific protein called connective tissue growth factor (CTGF) in the development of heart fibrosis. We will use an established animal model of heart fibrosis in which animals are given Angiotensin II (AngII). Using this model we will look at the levels of CTGF produced in heart tissue and characterize the possible mechanisms by which this molecule can recruit cells from the circulation that have recently been shown to be important in the eventual development of fibrosis. What is unique about our project is that we will be investigating role of CTGF in recruiting a novel cell that is now believed to come from the bone marrow and be responsible for the development of fibrosis. The name of this specialized cell is a fibrocyte or a fibroblast progenitor cell. We believe that knowledge gained from this study will lead to important treatment options for patients with heart fibrosis and heart failure. The only treatment of end stage heart failure remains heart transplantation but is limited to approximately 10 patients per year in Nova Scotia largely due to donor shortage.