Working out why blood vessels become leaky

Exploring the relationship between ezrin-radixin-moesin (ERM) proteins and NADPH oxidase 2 (Nox2) in modulating endothelial cell permeability in health and disease

Dr Aleksandar Ivetic and his colleagues at King’s College London are studying ways to prevent uncontrolled blood vessel leakiness, which can be life threatening. Humans are made up of 80% water, 10% of which is carried around our bodies by our blood vessels. The movement of fluid into and out of our blood is controlled by a single sheet of cells called the endothelium, which forms the lining of the inner walls of our blood vessels. The endothelium is made up of endothelial cells joined closely together like bathroom tiles. These endothelial cells have openings between them called junctions, which let fluid in and out of the blood. If blood vessels become abnormally leaky, for instance after a stroke or in lung injury, the surrounding tissue can become filled with fluid, which can be fatal. Blocking leaky blood vessels could be a new way to prevent this. In this project, Dr Ivetic wants to understand how endothelial cells open and close their junctions, and what goes wrong in disease to make them leaky. Using microscopes, he will study where and when two proteins, called ERM and Nox2, are located in endothelial cells, and work out how they ‘talk’ to one another to control the opening of the junctions between endothelial cells. This project will reveal more about the biological mechanisms that control blood vessel leakiness and could ultimately lead to the design of drugs to stop uncontrolled leakiness of blood vessels.