Group lead: Stuart Egginton
The formation of new capillaries from pre-existing blood vessels (angiogenesis) is a tightly controlled, multistep process involving extracellular matrix remodelling and endothelial cell migration & proliferation.
Angiogenesis is crucial during development, reparative processes such as wound healing, and physiological changes such as pregnancy. It also occurs in adult tissue such as cardiac and skeletal muscle in response to changing metabolic demand, e.g. during hypoxia or exercise training. An imbalance between pro- and anti-angiogenic factors leads to an inadequate or excessive vascular growth, which underlies many conditions that consume large amounts of NHS resources.
The widespread implications of controlling angiogenesis in situ has been a powerful incentive to stimulate angiogenesis in ischaemic muscle (e.g. peripheral vascular disease) by growth factor or gene therapy. Unfortunately, such angiotherapy has met with limited success, requiring a new approach. Our group uses physiological remodelling to devise targetted therapeutic repair of a pathologically damaged microcirculation. Also, examining how interactions between the cardiovascular and respiratory systems are controlled in hypothermia demonstrate how deleterious effects may be ameliorated, and lead to safe interventions involving therapeutic bradycardia. The multidisciplinary approach ranges from mathematical modelling and bioinformatic network analysis, through cell and molecular assays, to in vivo tissue performance and integrative function in a range of animal species and man. In exploring the limits to physiological adaptation, we are probing the origins of human morbidity.
Stuart Egginton (group lead)