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

Skeletal muscle has a remarkable capacity to meet changes in metabolic demand induced by altered levels of activity. One important response to endurance exercise training is a dramatic increase in muscle capillary supply seen in both animals and humans. For many disease conditions exercise is of major therapeutic interest, but what the optimal conditions are to maximise benefit for specific conditions is unknown. This project will concentrate on a major contributor to health improvement, an expansion of the capillary bed by the process of angiogenesis. Acute exercise increases expression of pro-angiogenic cytokines, but recent evidence suggests angiogenic inhibitors (angiostatic cytokines) are also increased. We aim to experimentally manipulate the balance of these factors to maximise efficacy of exercise therapy.

We will use exercise training, muscle overload and indirect electrical stimulation of locomotor muscles in rats and mice to elucidate the mechanisms of activity-induced angiogenesis. As low intensity training regimes often have little effect on capillarity, translational research would benefit from identifying the minimum amount of exercise required to generate significant health benefits. This will eventually allow us to develop effective angiotherapies targetted at specific pathologies by applying appropriate forms of muscle activity.

The project will apply a range of in vivo techniques, including surgical interventions (a Home Office licence will form part of the training), and assessment of muscle blood flow and performance. Other readouts will involve histological and molecular techniques to investigate the integrative response to altered muscle activity. This project will suit applicants with a life sciences background and specific interests in muscle physiology, angiogenesis, blood flow and/or oxygen transport.