How do blood vessel cells sense and respond to blood flow?

Defining the mechanisms of normal and pathological force sensing by endothelial cell adhesion complexes

The build-up of fatty deposits in arteries is much more likely to occur in the bends and branches of arteries, where blood flow is disrupted. Changes in flow can cause the cells that line the blood vessel wall (endothelial cells) to detach. Around a third of heart attacks occur when endothelial cells detach, as they can trigger the formation of a blood clot. This project is a partnership of two scientific teams: experts in how cells stick together (cell adhesion), and experts in endothelial cell biology. Together, they hope to discover the molecules that help endothelial cells stick to the vessel wall, and understand how these molecules change when blood flow is altered. Using an approach called proteomics – the study of all the protein molecules in a cell – they will identify important components of the ‘stickiness’ that keeps endothelial cells attached to artery walls in the heart. They will study this under normal and disease conditions, to understand how endothelial cells sense their environment and control their own stickiness. One of the main aims is to identify how harmful substances such as cigarette smoke affects endothelial cell health. This will highlight ways to reduce damage from these substances and stop endothelial cells detaching, reducing risk of a heart attack.