Understanding how to keep the blood vessel barrier intact

Dual function of the GTPase activating Ppotein ARAP3 in the regulation of endothelial permeability

The cells that line our blood vessels (called endothelial cells) form an important barrier that contains blood inside the vessels and controls the entry of substances from the blood into surrounding tissues. Inflammation of the blood vessels weakens this barrier, causing blood to leak into tissues, causing serious complications in organs such as the lungs. Treatments to help restore this barrier a currently limited. As well as endothelial cells, neutrophils (the most common type of immune cell) are important for maintaining the blood vessel wall. ARAP3 is a molecule present in large amounts in both of these cell types and is suspected to play a major role in controlling the tightness of the blood vessel barrier. Dr Sonja Vermeren intends to test this by removing ARAP3 in endothelial cells or neutrophils and monitoring how this influences the blood vessels barrier. She will also test the blood barrier leakiness in mice with mild inflammation and in mice which lacking ARAP3 in the endothelial cells or the neutrophils. This project will help us to better understand how the blood vessel barrier is regulated by different cell types. There are currently few treatments for people affected by inflamed and leaky blood vessels so this study might identify ARAP3 as a potential therapeutic target to help those with this condition.