Understanding how a genetic fault leads to blocked arteries

Investigation of the role of Bcar1/p130Cas in atherosclerosis

Scientists have previously discovered that changes to the Bcar1 gene are linked to the development of atherosclerosis – the build-up of fatty deposits in blood vessels. But little is currently known about how these genetic changes cause the formation of fatty deposits, or which cells in blood vessels are affected. In this project, Professor Ian Zachary and his team will study the Bcar1 gene and its protein product, called p130Cas, in mice. They will investigate how the two play a role in atherosclerosis. Professor Zachary thinks that Bcar1/p130Cas might be involved in controlling the movement of blood vessel cells that are involved in the thickening of blood vessel walls. In mice that are prone to the formation of atherosclerosis, they will delete the Bcar1 gene in blood vessel cells and look at how this affects the development of atherosclerosis. They also plan to investigate the amounts of the Bcar1/p130Cas protein in human atherosclerotic vessels. Finally, they will look at how naturally occurring changes to the Bcar1 gene affects blood vessel growth and function. They will do this by altering the gene in cells grown in the lab, and by studying the naturally occurring gene change in blood vessel cells from human donors.