How do heart forming cells in the womb influence congenital heart defects and adult heart disease?

Embryonic lineage in development, malformation and disease of the cardiac outflow (renewal)

Sometimes, the aorta and pulmonary artery (the arteries that carry blood away from the heart to the lungs and the rest of the body) do not properly form in the foetus. Some of these malformations are life-threatening at birth whereas others cause no problems for many years. People with milder abnormalities are still predisposed to serious heart and circulatory diseases in later life. These include valve infection (endocarditis), restricted blood flow to the aorta (aortic stenosis) and aortic aneurysm (where the aorta wall ‘balloons’ and can burst). All of these conditions need treatment and can result in sudden death in some cases. Professor Deborah Henderson and her team at the University of Newcastle-upon-Tyne are studying how different populations of heart forming cells contribute to heart development, and what can go wrong and lead to the main arteries forming incorrectly. They have identified certain cells and genes that ensure the arteries form correctly, and found that the location of the cells also determines the degree of malformation that results. This team will research why these abnormalities occur and how they can lead to heart disease in adult life. In mice, they will map out where different cells in the embryo go as the arteries mature, and find out if incorrect patterns of development can explain the different types of artery malformations that develop later. They will breed mice with artery malformations to find out if the incorrect patterns explain how disease progresses, and if they determine responses to treatment. They will then find out if the same happens in people to support development of better therapies in the future.