Interactions with VEGF – a potential protein for mending broken hearts

Mechanisms and biological roles of the VEGF receptor/neuropilin signalling axis in cardiovascular health and disease (renewal)

Heart and circulatory disease is Britain’s biggest killer – in 2009 it was responsible for one in three deaths. Endothelial cells line our blood vessels ensuring that our circulatory system functions normally. It is often disruption of these cells that can lead to disease and they may also have a role in mending broken hearts damaged by heart attack. A protein known as VEGF-A or VEGF (vascular endothelial growth factor), binds onto the surface of endothelial cells via receptor molecules present on the cell surface. It controls the formation of blood vessels and could therefore play an important role in regenerating arteries that nourish the heart in heart disease patients. But to make this possible further research is needed, partly because when too much VEGF is present, it can contribute to disease. Professor Ian Zachary and his team will investigate molecules on the surface of endothelial cells that interact with VEGF and its receptor, in particular a molecule called Neuropilin 1 (NRP1). NRP1 is essential during the development of the heart and circulatory system in the foetus. It is currently believed that NRP1 plays an important role in how VEGF influences processes inside endothelial cells. Prof Zachary and his team will test this – in human, mouse and zebrafish cells – and try to better understand the role played by VEGF and NRP1 in generating new blood vessels. This will provide new insights into how and what happens when these molecules interact with endothelial cells to create new blood vessels and also assess any damaging effects caused by having too much VEGF. Ultimately it could lead to more effective ways to grow new blood vessels in diseased hearts.