Animal models of exercise therapy: mechanisms of activity-induced angiogenesis

Skeletal muscle is spatially heterogeneous in muscle fibre type composition and microvascular supply. The capacity to quantify this heterogeneity in skeletal muscle is not routinely performed for it’s a laborious and time consuming technique. We have developed a high throughput data pipeline that utilises the simultaneous immunohistochemical labelling of muscle fibre type and microvascular supply, as an input for a semi-automated analysis software package that allows for the analysis of fine morphometric indices of fibre type composition and the interactions with microvascular supply. We have successfully shown that regional variation in fibre type composition impacts the functional characteristics of a muscle. After successful characterisation of regional heterogeneity in both structure and function we sought to establish their influence in physiological (adaptive) angiogenesis. Utilising animal angiogenic models we have shown that shear stress driven angiogenesis is principally a stochastic response that does not promote improved oxygen delivery when we analyse the spatial heterogeneity of the neovasculature. Conversely, skeletal muscle overload (abluminal stretch of microvasculature) increases the homogeneity of the oxygen supply area of the capillary bed, suggesting a tissue driven angiogenic response that is not evident in shear stress. Spinal cord injury induced rarefaction of the capillary bed attempts to maintain a homogeneous distribution of fibre size and capillary supply. The combination therapy of epidural stimulation and locomotor training can ameliorate the phenotypic change and rarefied capillary bed seen with spinal cord injury to that of intact levels. Endurance and resistance exercise have a largely similar global genomic response following a chronic training regime, which we are able to replicate in animal models of exercise through indirect electrical stimulation. The shear stress and muscle overload driven angiogenic response have distinctly different angiogenic pathways that contain no commonly expressed networks