Investigating the Impact of Environmental Stressors on Skeletal Muscle Angio-Adaptation

Skeletal muscle angio-adaptation refers to coordinated molecular and cellular events that regulate the expansion (angiogenesis) or regression of the muscle capillary network. The influence of environmental stressors (hypoxia, cold-stress) on skeletal muscle angio-adaptive responses are less understood in comparison to exercise-training or diseased states. This thesis addresses the influence of hypoxia and cold-stress on skeletal muscle angio-adaptation through a literature review and original research, respectively. After reviewing the literature, ambient hypoxia alone may be insufficient in improving muscle capillarization, however ambient hypoxia superimposed with exercise enhances the angiogenic response of exercise-training. In-vitro, the effect of cold-stress with respect to the angiogenic relationship between the myocyte and endothelial cell was investigated. Cold-stress reduced the secretion of angiogenic molecules from the myocyte. Furthermore, cold-stress abrogated endothelial cells proliferation and attenuated VEGFR2 activation. Endothelial cells pre-conditioned to cold-stress and challenged for migration in re-warming conditions however, exhibited an enhanced migratory responsiveness.