Grant: Discovery Grants Program - Individual

Skeletal muscles represent more than 40% of our body weight and participate in important physiological functions such as body mobility, force and movements production, thermoregulation, or the regulation of blood glucose levels. Capillaries, our smallest blood vessels, represent an important determinant of muscle functions: they ensure a good delivery of oxygen and nutrients to the contracting muscle cells. These muscle capillaries are mainly composed of endothelial cells and are very adaptable. Physical exercise is a powerful stimulus that leads to the formation of new capillaries in our skeletal muscles. This biological process, named angiogenesis, is tightly regulated by stimulatory and inhibitory molecules essentially produced and released by the contracting muscle cells to stimulate the neighbouring endothelial cells to form new capillaries. My research program investigates the cellular and molecular mechanisms that regulate skeletal muscle angiogenesis. I am particularly interested in understanding how the contracting muscle cells stimulate endothelial cells. In this context, my research proposal aims to investigate if the contracting muscle cells produce molecules named angiomiRs in response to exercise to stimulate the endothelial cells. Micro-RNAs (miRs) are short RNA molecules that regulate gene expression. AngiomiRs specifically refer to miRs that can regulate endothelial cells activity and angiogenesis. I will also determine if the combination of exercise with hypoxia (lack of oxygen like during altitude) or cold exerts a greater stimulatory effect than exercise alone. Research suggests that hypoxia and cold exposure could indeed enhance the stimulatory effect of exercise on muscle angiogenesis. Analyses will be mainly performed in cultured muscle cells and endothelial cells as well as using rodent models. Cell culture experiments will assess the impact of cell contractile activity (induced by electrostimulation) alone or combined with hypoxia and cold on the production of angiomiRs by the muscle cells, and whether these angiomiRs stimulate endothelial cells. We will also use these cell models to identify the underlying mechanisms that regulate the production of angiomiRs by muscle cells. The physiological relevance of this angiomiR-based mechanism will be determined using rodent models of exercise-induced muscle angiogenesis combined or not with hypoxia and cold exposure. By discovering how angiomiRs could regulate muscle angiogenesis my research program will generate new knowledge in the fields of muscle and vascular biology, exercise and environmental physiology. Our understanding of the combined effects of exercise and environmental stressors on muscle angiogenesis could have direct applications for elite Canadian athletes to develop new training protocols as well as for outdoor recreationists. My research program will also continue to train High Qualified Personnel as the new generation of Canadian researchers.