Understanding and targeting cell senescence in atherosclerosis

Causes, consequences and therapeutic potential of cell senescence in atherosclerosis (renewal)

Atherosclerosis is the build-up of fatty deposits called plaques in blood vessel walls. When these plaques rupture and cause a blood clot this can lead to a heart attack or stroke. The plaques are usually protected by a ‘cap’ containing vascular smooth muscle cells (VSMCs) which make up part of the wall of blood vessels. This cap prevents the plaque from rupturing. In mature plaques, the VSMCs can be ‘senescent’. This means they don’t grow or divide and they can trigger inflammation. All of this makes the plaque unstable and more likely to rupture. Senescent cells are normally cleared from the body by the immune system. But in atherosclerosis, senescent VSMCs manage to escape this process. This programme will explore the role of senescent VSMCs in atherosclerosis using human cells and mice. Specifically, it aims to understand (a) the mechanisms and consequences of VSMC senescence in atherosclerosis, (b) how senescent VSMCs are cleared from the body, and (c) whether senescent VSMCs could be specifically targeted with drugs to reduce atherosclerosis. The research will provide new insights into how common senescent VSMCs are, what causes them and how they influence atherosclerosis. It could also show whether drugs that remove senescent cells or prevent them from causing inflammation could be promising for people with, or at risk from, heart and circulatory disease.