Searching for a safer anti-clotting drug by studying a protein called Factor XII

Conformational regulation and cardiovascular disease dysregulation of Factor XII (Mr Alexander Brown)

People who have survived a heart attack or stroke tend to be at high risk of having another one. To try to prevent a repeat event, doctors prescribe certain medicines. These often include anticoagulant, also called anti-clotting, drugs such as heparin or warfarin. These are drugs that help to prevent heart attacks and strokes by stopping blood from clotting in the arteries feeding the heart and the brain. However, this anti-clotting effect occurs all over the body, leaving people at greater risk of dangerous internal bleeding. Safer medicines are needed to replace today’s anticoagulants. These researchers are studying a protein called Factor XII, which has been shown to play a key role in blood clotting and could be a target for new medicines that safely reduce the risk of heart attack and stroke. The Nottingham team will study in detail the 3D shape of Factor XII and how it interacts with other proteins to do its job. We know that Factor XII has a different shape when it’s active compared to when it’s inactive. The team will uncover how this change occurs and whether this is altered in people at greater risk of heart disease. This structural information could provide clues towards a new kind of treatment to control blood clotting safely.