Reprogramming the immune response to heart injury

The role of endothelial cell derived extracellular vesicles in monocyte mobilisation and activation in acute myocardial infarction

After a heart attack, immune cells called monocytes rush into the heart from the spleen and become ‘switched on’ along the way. Normally, the immune response caused by monocytes is a positive effect that helps fight infections. But when this happens in the heart, it can lead to permanent damage. Professor Choudhury’s lab has previously shown that tiny particles released from cells – known as vesicles – are involved in the activation and mobilisation of monocytes after a heart attack, but the exact mechanisms involved are not fully understood. Following a heart attack, the number of vesicles in the blood increases, particularly those released by the cells lining the blood vessels. In this project, the researchers hope want to establish how heart injury causes an increase in the number of vesicles released. In addition, as vesicles play an essential role in helping cells communicate with each other, they will study which molecular messages they are carrying. Finally, they will use an innovative ‘gene editing’ technique called CRISPR to alter the molecular messages within the vesicles. The aim is that, by reprogramming them in this way the vesicles can help to send signals which help heart repair, rather than switching on damaging immune responses.