Can we assist a natural ‘master regulator’ of blood vessel health to treat heart disease?

Validation of the transcription factor erg as a target for the prevention and treatment of cardiovascular diseases

The cells that make up the innermost lining of our blood vessels are called ‘endothelial cells’. They actively influence all sorts of functions including how permeable the vessels are, how they grow, and the tendency for blood to clot within them. In coronary heart disease, which leads to angina and heart attack, we know that the coronary artery endothelial cells aren’t functioning properly. It’s thought that protecting the health of these cells with medicines, or even enhancing their ability to ‘look after’ blood vessels, might be a new route to prevent or treat heart disease. Professor Anna Randi’s team at the BHF Centre for Research Excellence at Imperial College London, will investigate ways to protect endothelial cells by investigating a protein called Erg, which seems to be a linchpin for many of the cells’ functions. Erg has the ability to turn on a combination of genes in the endothelial cell. This results in different proteins being made, all of which have specific functions – some might turn on other genes, some might send a signal to a neighbouring cell, some might sit on the cell’s surface to attract molecules in the bloodstream. In these ways and many more, Erg can kick-off multiple processes in the endothelial cell, and is known as a ‘master regulator’ for this reason. The team at Imperial will use a combination of molecular techniques to unpick exactly how Erg works, what its effects are, and how it is regulate. Their goal is to find out which of Erg’s effects are most important for health and identify ways that we can modify or enhance these to prevent or reverse disease in our arteries.