Identifying new targets for the prevention and treatment of atherosclerosis

Identification of novel mechanoresponsive signalling networks that control endothelial cell injury and activation

Patients with atherosclerosis have damaged arteries, caused by a gradual build-up of fat within the artery wall. The body’s immune cells invade the artery wall to remove the fat but can get trapped there, forming a plaque. Plaque is made up of fat, cholesterol, calcium, and other substances found in the blood. Some plaques become inflamed and unstable, and can break open, triggering a blood clot to form on the plaque’s surface. If the clot becomes large enough and blocks oxygen-rich blood supplying the heart muscle or brain, it can lead to a heart attack or stroke. Atherosclerosis begins when cells lining the inner surface of arteries called endothelial cells become injured. The main process responsible for initiating this injury is inflammation (the immune system’s response to infection and injury), but a process called apoptosis (where cells ‘kill’ themselves) is also involved. Although we know these processes occur predominantly in areas of arteries where there is disturbed blood flow such as at branches and bends, we do not understand how the two processes arise. Professor Paul Evans and researchers at the University of Sheffield recently found that different blood flow patterns switch genes controlling these processes on and off in endothelial cells in the aorta - the main artery pumping blood from the heart to the body. The BHF has now awarded a grant to the Sheffield researchers to study more about these genes and how they cause endothelial cell injury in particular areas of arteries. This work will tell us more about how atherosclerosis begins, why certain areas of arteries are more susceptible to damage and which genes might be protective. Ultimately it may reveal new targets for drugs to prevent or treat atherosclerosis.