Grant: Operating Grant

Heart disease is the leading cause of death in Canada. It can be caused by multiple risk factors, which cause inflammation by activating blood cells, and damage blood vessels that supply the heart with oxygen. Such damage causes hardening of the arteries by plaque formation (atherosclerosis) and symptoms such as chest pain. This may cause complete blockade of the artery by a blood clot (thrombus) composed of blood cells and proteins. Unfortunately, current drug treatments do not prevent completely or limit the progression and the occurrence of narrowed and blocked heart blood vessels. Actually, a subset of progenitor cells called endothelial progenitor cells have shown promising results in repairing the damaged arteries and in limiting the reactions of platelets, the principal blood cells involved in blood clots. However, some inflammatory molecules in blood, such as CD40 ligand, may affect the function of endothelial progenitior cells and their capacity to reduce blood clot formation. The objectives of our research program are: 1) Determine that CD40 ligand reduces the anti-platelet activities of endothelial progenitor cells; 2) Identify the biochemical reactions involved in the action of CD40 ligand on endothelial progenitor cells; and 3) Demonstrate that the anti-blood clot potential of endothelial progenitor cells is impaired by elevated blood levels of CD40 ligand in an animal model of blood clot formation. Our experimental approaches include molecular and pharmacological tools which involve in vitro experiments with isolated blood cells, as well as in vivo studies with a clinically relevant animal model of heart vessel disease. This project is very important for many fundamental and clinical reasons. We intend to identify new mechanisms linking blood and progenitor cells and damaged vessels. These insights should enable us to identify new drugs and to propose innovative approaches in the clinical management of heart diseases.