Endothelial cells (EC) form the inner lining of blood vessels and are essential for their function and homeostasis. Endothelial cells are highly heterogenous and can therefore behave very differently depending on the local environment. These differences are essential to form new blood vessels in areas of need, to adapt vessels to changes in the local environment, and to create and maintain different branches of the vasculature, which includes arteries and veins.
Identifying how these ECs behave in different situations is vitally important to understanding how the body attempts to repair itself after injury through the formation of new blood vessels, what can go wrong and how we can try to manipulate the behaviour of ECs to facilitate repair.
Associate Professor Sarah De Val’s lab aims to identify and describe the regulatory pathways responsible for controlling different aspects of EC behaviour. The team's recent research has characterised multiple independent regulatory pathways, and in order to do this, they have generated a number of novel enhancers: reporter transgenic mouse lines.
“With Prof Nicola Smart, we have already successfully used these transgenic models to investigate the regulatory pathways controlling different types of vessel growth in the heart, uncovering unexpected differences between the pathways involved in development, quiescence and response to injury” (Prof De Val). These findings could hold the key to understanding exactly how these pathways operate when the heart is damaged.
Prof De Val, in a close collaboration with Dr Gillian Douglas from the Radcliffe Department of Medicine, has now been awarded a £50,000 grant from the University of Oxford’s John Fell Fund to allow her to expand this investigation of EC regulatory pathways into different cardiovascular disease states.To do so, they plan to analyse and gather data from multiple models of common cardiovascular diseases in which incorrect EC behaviour is a key disease modulator.
If they can establish the mechanisms behind EC dysfunction, their research could pave the way for understanding why these diseases develop and potentially inform the development of future therapeutic or even preventative strategies targeting the independent pathways.