Halting inflammation after a heart attack to prevent heart failure

Attenuating cardiac inflammation and remodelling by targeting the Tenascin C - TLR4 axis

After a heart attack, inflammation plays an important role in the healing and repair process that follows. However, long term inflammation can lead to changes in the way the heart is structured, a process called cardiac remodelling, which can later lead to heart failure. Why this happens, isn’t fully understood. A molecule called tenascin C is known to be switched on for a short time after a heart attack, and is turned on continuously in chronic cardiac diseases. Increased levels in the blood and heart are also linked to increased remodelling and the severity of heart failure. Dr Azhar Maqbool’s team at the University of Cambridge has previously shown that tenascin C increases the amount of substances which promote inflammation in heart cells by switching on a molecule called TLR4. In this project, the team will use a new approach called ‘peptide display technology’ to stop tenascin C switching on TLR4 by blocking it’s switch site. If it works, it might be possible to design new drugs to block tenascin C, prevent inflammation and help the heart recover better after a heart attack.