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

Peripheral artery disease (PAD) is a degenerative vascular condition that affects a growing percent of the Canadian population. This disease is characterized by arterial blockage that results in extensive reductions of blood flow to the muscles of the lower leg (ischemia). Individuals with PAD suffer from an increasingly severe condition that ranges from mild leg pain upon exertion to gangrene that requires limb amputation. PAD patients with type-2 diabetes experience a more severe prognosis and reduced life expectancy, but the reasons for these poor outcomes are not known. My research aims to explain why diabetic PAD patients suffer from more severe disease than non-diabetic patients. Specifically, I will focus on factors that affect the number of small blood vessels within muscle, because they are important determinants of disease severity. A key unanswered question is why the growth of small blood vessels, angiogenesis, does not occur in the ischemic muscles of PAD patients. I hypothesize that an increased presence of anti-angiogenic factors limits blood vessel growth and contributes to disease severity. In support of this, I was involved in a study that identified higher levels of an anti-angiogenic factor (FoxO1) in the muscle of PAD patients. Levels of other anti-angiogenic factors are yet to be determined and it is not known whether these factors are elevated further in the ischemic muscles of diabetics. Using both animal models of PAD and clinical patient samples, I will identify and compare the levels of these anti-angiogenic factors within the ischemic muscles of diabetics and non-diabetics. This knowledge will enable us to identify specific molecular factors that allow us to predict an individual's capacity to stimulate angiogenesis. Furthermore, it will identify possible therapeutic factors that improve the quality of life and functional independence of PAD patients, particularly those that also suffer from type 2 diabetes.