Inhibiting Wnt signalling as a strategy to treat abdominal aortic aneurysm

Suppression of Abdominal Aortic Aneurysms via Porcupine Inhibition (Mr Alexandros Somos)

An abdominal aortic aneurysm (AAA) is a ballooning of the aorta, the body’s main blood vessel that passes from the heart through the trunk of the body. It’s an extremely dangerous condition; it can develop without symptoms and can burst, causing sudden death. AAA is most common in older men, so a screening programme is in place to detect aneurysms in males over 65. However, if an aneurysm is found, currently the only option is surgery, which carries risks. In AAA, the artery weakens partly due to both the death of cells in the artery wall and inflammation. Professor Sarah George and her team at the University of Bristol have discovered that a specific set of molecules ‘talk’ to each other as part of the so-called Wnt pathway, which is important in the development of aneurysms. A protein called Wnt is released from cells, kicking off a process that can alter the structure of the artery wall. A study in mice showed that stopping this pathway prevented aneurysm formation, but the chemical used to do this is not suitable as a medicine. These researchers will now test another approach to blocking the Wnt pathway, by stopping a protein called Porcupine that allows Wnt to be released from cells. They’ll study its effect in mice and how Wnt signalling changes in samples of AAA arteries donated by patients having surgery. It is hoped this research could lead to a vital new approach to treating this dangerous condition.