Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Aging increases the susceptibility to develop cardiovascular diseases (CVD). Endothelial cells (ECs) compose the endothelium, which cover the lumen of the artery. Aging of ECs is divided in two phases: maturation and maintenance. The maturation part consists in the growth and development of the endothelium, including antioxidant defenses that protect from excessive production of free radicals also called reactive oxygen species (ROS). ROS are essential for cell function and are byproducts of energy synthesis within the cell. An imbalance between ROS production and their enzymatic degradation lead to oxidative stress, which is implicated in pathologies and is of tremendous importance in the aging process. During the maintenance phase, ECs preserve their function developed during maturation by repairing damages induced mainly by ROS. Both phases are believed to be under the control of a protein known to be implicated in cancer, the tumor suppressor p53. My hypothesis is that p53, by sensing ROS, regulates accordingly the level of expression of antioxidant enzyme. To address this hypothesis, we will use mouse models (control and genetically engineered to inactivate p53). These mice will be treated with an antioxidant to prevent oxidative stress and we will follow expression and function of antioxidant enzymes. We propose that the construction of an efficient oxidative stress defense system during the maturation phase is of extreme importance, and that p53 is a major switch. Well-developed defense against ROS during maturation can delay onset of aging symptoms during the maintenance phase. Better understanding of these process will allow us to pinpoint molecular pathways implicated in aging and might help us to propose new targets to design pharmaceuticals tools slow CVD progression.