Angiogenesis in health and disease 2020

Rationale: Cardiovascular disease and diabetes have been shown to adversely affect muscle function, leading to exercise intolerance (reduced physical activity levels), but detailed mechanisms and effective interventions are lacking.

In both cases, a better understanding of the cellular, biochemical and tissue interactions involved will aid in developing specific therapies to reduce patient morbidity. We use a more modest, potentially therapeutic intervention (muscle overload, such as seen with weight training) as an experimental test of the muscle capacity to adapt to normal challenges of daily living, as this has been suggested to be influenced by the blood supply in situations of severe pathology (involving gross muscle damage).

Plan of work and impact of our studies: We will explore how skeletal muscle responds to physiological or pathological challenges, and how the smallest blood vessels may influence the outcomes. This will allow us to better understand how outer tissue (muscle) dysfunction may contribute to exercise intolerance associated with central (cardiovascular) limitations. We aim to determine if the associated muscle atrophy (i.e. muscle wasting, and accompanying weakness) may be reduced. This should provide evidence that muscle hypertrophy may offer a novel therapeutic approach to rehabilitation.

Animal welfare: We are using animals previously demonstrated to exhibit similar mechanisms of muscle hypertrophy/atrophy as seen in humans, which will allow us to explore new ways of supporting exercise tolerance in conditions where mobility is limited. For some animals, they will be put to sleep and one hindlimb muscle removed; this parallels the situation in humans following disease, cancer or a traffic accident. We take care to administer pain relief after surgery, and the animals recover very quickly - indeed, they have been observed engaged in normal social interaction and activity patterns within 24 hours, suggesting there are no serious impediments to locomotion or routine activity.

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