How is a molecule called beta-catenin involved in atherosclerosis?

Is ß-catenin a master regulator of mechanical signalling in the endothelium?

BHF Intermediate Basic Science Research Fellow Dr Christina Warboys is studying atherosclerosis, when arteries become furred up with fatty plaques and narrow. If the plaque ruptures, a blood clot can form and lead to a heart attack or stroke. Atherosclerosis often occurs in areas of blood vessels that are exposed to disturbed blood flow. This disturbed flow can alter the function of the endothelial cells lining the vessel wall, leading to vessel wall damage, an early stage of atherosclerosis. We don’t understand how endothelial cells sense and respond to blood flow, but there is some evidence that a protein called beta-catenin builds up inside cells exposed to disturbed blood flow. In this project, Dr Warboys will study what happens to beta-catenin inside endothelial cells that have been exposed to disturbed flow as she thinks it may explain why endothelial cell behaviour is altered. She will work out how the protein interacts with other proteins and moves to the ‘genetic hub’ of the cell, the nucleus, in response to disturbed blood flow. Once in the nucleus, beta-catenin may switch on genes controlling cell functions associated with heart and circulatory disease, causing inflammation or other processes that lead to atherosclerosis. This research will improve our understanding of the processes that control atherosclerosis development in certain areas of blood vessels. It may reveal new therapies that can prevent or slow fatty plaque formation.