Grant: Doctoral: Vanier Canada Graduate Scholarships

Coronary heart disease is the second leading cause of death in Canada, and results from the build-up of plaque in the coronary artery causing reduced blood flow to the heart. This can lead to a heart attack when the coronary artery is completely obstructed. A heart attack is usually treated by inserting a stent at the site of occlusion to restore blood flow and oxygen delivery to the heart. However, this sudden reintroduction of oxygen to previously deprived tissue can actually cause the heart cells to die in a process called ischemia reperfusion injury. Recent clinical trials of promising pharmaceuticals have failed to find any preventative therapies for this condition. Apelin is a mammalian peptide hormone that exerts a wide range of protective effects in the heart. Importantly, apelin has been shown to be protective against ischemia reperfusion injury, suggesting that targeting this hormone system may serve as a potential therapy for this deadly condition. There are three major types of apelin circulating in human plasma, each triggering slightly different protective physiological effects in the heart. However, apelin is degraded rapidly in the bloodstream. For apelins to be used as drugs to treat heart disease, the chemical structure of this hormone must be altered to achieve increased stability in the blood, while still maintaining potency and protective effects in the heart. My project proposes to study the way that the different types of apelin peptides direct differing effects in the heart, and will use the information learned to develop new analogues of apelin for use as drugs to treat ischemia reperfusion injury. This collaborative, interdisciplinary project combines chemistry, biology, and physiology in order to solve a major challenge to our healthcare system, and produce practical solutions to be used by both patients and physicians.