Studying the release of von Willebrand factor as a target for future medicines

Controlling the haemostatic response: Novel regulatory mechanisms for von willebrand factor secretion from endothelial cells

A BHF-funded team based in London are studying how to prevent harmful blood clotting without preventing helpful clots. The body’s response to injury needs to be rapid to prevent blood loss and minimise the chance of infection. Cells that line blood vessels contain packages of pre-made clotting factors that are released into the blood vessel to start the blood clotting process and recruit immune cells to fight infection. However, blood clotting can also be dangerous, for instance, when it occurs in diseased coronary arteries, it can cause a heart attack. Finding ways to limit dangerous blood clotting without slowing down the response to injury is a major goal of research. An inappropriately high level of von Willebrand factor (VWF), one of the pre-made clotting factors, is associated with heart disease and stroke. This team have previously discovered that the release of VWF requires an apparatus to squeeze it out of the cell. They have developed a way to identify the components of this cellular apparatus, and in this project they will take that work forward. By identifying all the molecular pieces of the apparatus needed to release VWF, and working out which are the most important components, they will spot potential targets for new medicines. If a drug could be designed to block the VWF-releasing apparatus, it could be a new approach to treating heart disease without compromising the normal immune response.