Revealing the genetic faults responsible for the most common aortic valve defect

Development and disease of the arterial valves

At the entrance and exit of each of the four chambers of the heart are valves, which open and close quickly between heartbeats to stop blood flowing backwards. If the heart valves are faulty – if they don’t open properly or are leaky - they place a strain on the heart and this can lead to heart failure. The aortic valve is found at the exit of the heart through which blood is pumped around the body. Abnormalities in this valve affect around one per cent of people. The commonest abnormality, bicuspid aortic valve or BAV, can be present in newborn babies but often doesn’t cause problems until middle age. Defects can also run in families and researchers think they are caused by variations in genes involved in the valve’s development in the womb. However, we don’t yet fully understand how the aortic valve forms and so cannot be sure if these changes in the genes are truly responsible for the faulty valve. In this project, Professor Deborah Henderson and her team in Newcastle will find out how ‘normal’ aortic valves are formed in mice and zebrafish. They will then see how mutations similar to those seen in people with BAV disrupt these processes to see if it results in changes in the aortic valve. This could help identify which of the suspected genes are truly important in BAV, and so help doctors to predict possible outcomes in their patients, and help them to understand the risk to extended family members.