The role of histones in reperfusion injury following a heart attack

The role of extracellular histones in myocardial ischaemia-reperfusion injury (Dr Mohammed Shah)

Professor Derek Yellon and his team at University College London are investigating how the release of proteins, called histones, leads to damage in the heart after a heart attack, and how we could stop it. A heart attack occurs when an artery supplying blood to an area of heart muscle becomes blocked. While the artery is blocked, the heart muscle is being starved of blood and oxygen, which causes damage to this part of the heart. For that reason, doctors aim to open the blocked artery as quickly as possible, but this sudden reinstatement of blood flow – known as reperfusion - also causes inflammation and further damage to the heart muscle. Professor Yellon’s team want to reduce the amount of heart muscle that dies as a result of a heart attack and reperfusion, through controlling this inflammatory response. Key molecules involved in this process are histone proteins. They are normally found with our DNA, packaged-up safely in the cell nucleus, but are released when cells die. The team will study how histone release causes damage and will use newly-designed drugs, which can remove histones, to see if they can protect the heart from injury in rats. In the future such medicines could become a treatment to limit heart damage caused by heart attack and its treatments.