How dying cells inflame fatty plaques in atherosclerosis

The role of IL-1R2 in controlling IL-1-driven inflammation in atherosclerosis

Heart attacks are caused by rupture of abnormal thickenings (atherosclerotic plaques) that form within the coronary artery wall, leading to clots that block blood flow. One cause of plaque rupture is thought to be the loss of muscle cells, called vascular smooth muscle cells (VSMCs), which normally form a meshwork that strengthens the plaque. Sometimes VSMCs die by a process called necrosis, which results in the cell bursting and releasing its contents. VSMC necrosis may cause inflammation, destruction of the plaque meshwork, more VSMC death and eventually plaque rupture. In this Senior Basic Science Fellowship, Dr Murray Clarke at the University of Cambridge will investigate how VSMC necrosis causes inflammation. He is particularly interested in the role of a protein called interleukin-1 alpha, which is released from necrotic VSMC. An in depth understanding of how inflammation is caused in atherosclerosis will help guide the development and testing of new drugs to treat coronary heart disease.