Protecting the heart against ischaemia-reperfusion injury

Role of cyclic AMP/PKA/Epac signalling in cardioprotection 

Professor Saadeh Suleiman is working out how we can protect the heart from further damage when blood flow is restored after ischaemia; this is when the heart is deprived of blood carrying oxygen, such as during a heart attack. The only way to protect the heart muscle is by rapidly restoring blood flow, which is called reperfusion. But restoring blood flow can also causes damage, which is called reperfusion injury, and in some cases this may be fatal. Professor Suleiman and his team have found that consecutively treating the heart with two drugs called isoprenaline and adenosine protects against the damaging effects of ischaemia and reperfusion. Isoprenaline increases levels of a molecule called cyclic AMP (cAMP). cAMP then activates an enzyme called protein kinase A (PKA), which helps protect the heart against damage. A second enzyme called Epac is also activated by cAMP. Professor Suleiman has found that activating Epac also enhances the protection given by PKA. In this project, the researchers will investigate how activating PKA and Epac by cAMP protects the heart against ischaemia-reperfusion injury. This research will improve our understanding of the ways in which the heart protects itself during ischaemia and reperfusion and may identify new targets to treat to prevent heart injury after loss and restoration of blood supply.