In collaboration with Boehringer Ingelheim and EI Lilly, the Heart and Stroke/Richard Lewar Centre of Excellence in Cardiovascular Research (HSRLCE) ran an HSRLCE/BI-LILLY Cardiometabolic Award competition in August 2018.
The goal of the award was to fund innovative ground-breaking clinical research projects in cardiometabolic disease, specifically the link between cardiovascular disease and diabetes. The award was open to qualified Canadian MDs or PhDs who were within the first five (5) years of their first faculty appointment at a Canadian academic institution and are eligible to conduct clinical research.
Two awards were given out:
- Dr. Cynthia Luk, Scientist at St. Michael’s Hospital: 1st place winner – $25,000 award
Project Title: The Role of Adipose Tissue Signaling in the Pathogenesis of Atherosclerosis
- Dr. Charles de Mestral, Vascular Surgeon-Scientist at St. Michael’s Hospital: 2nd place winner – $20,000
Project Title: Reducing Amputation from Diabetes and Peripheral Arterial Disease through Regional Foot Care and Amputation Prevention Pathways
About the Projects:
Cardiovascular disease, which includes heart attacks and strokes, is the leading cause of death worldwide. The major process underlying cardiovascular disease is the buildup of fatty plaque in arteries, knows and atherosclerosis. In the past two decades, studies have shown that inflammation plays a major role in the development of atherosclerosis. Fat is increasingly recognized as a highly dynamic organ uniquely capable of massive growth with obesity, and can play an important role in inflammation, especially weight gain. Furthermore, brown or beige fat can be highly metabolically active with the potential to prevent the development of atherosclerosis. The signalling pathways regulating fat and their role in atherosclerosis remain unclear.
Caspase 8 is a signaling protein best known for its role in cell death, but there is mounting data to suggest it can have other functions. Our preliminary data suggests that caspase 8 is important in fat. Specifically, caspase 8 appears to increase in fat and weight gain, and can promote inflammation and decrease the role of fat cell caspase 8 in the development of atherosclerosis.
To best study whole body physiology, we will use mice susceptible to atherosclerosis with caspase 8 knocked out only in fat. We will study these mice to determine the role of signaling in fat on inflammation, energy expenditure, and ultimately plaque growth in arteries. This work will uncover a new link between fat and metabolic disease, improving our understanding and identifying new pathways we can target for the treatment of prevention of cardiovascular disease.
Dr. de Mestral’s
Leg amputation is a devastating complication of diabetes and poor blood circulation. Unfortunately, regular foot care and amputation prevention efforts remain shockingly disjointed across Ontario. The end-goal of the proposed research is to reduce the number of amputations by informing the development of regional foot care and amputation prevention pathways for patients with diabetes or peripheral arterial disease. Big data analysis will clarify the region-specific burden of amputations as well as the real-world clinical and economic evidence-basis for system improvement to integrate sustained prevention efforts, multidisciplinary care of foot complications and rehabilitation.