Bolstering the heart’s defences against chemotherapy and diabetes

Impaired Rap1 signalling increases mitochondrial reactive oxygen species production and susceptibility to cardiac arrhythmias: implications for drug therapies and disease mechanisms (renewal)

In the cells of our body, day-to-day processes cause the creation of ‘reactive oxygen species’ (ROS) – toxic molecules that can cause damage to our cells. In the heart, excessive ROS production can cause dangerous irregular heart rhythms. Our bodies have coping strategies to reduce ROS in our cells, and Professor Steele has discovered one of these in heart muscle cells. Unfortunately this defence mechanism, known as Epac-Rap1, is the target of emerging chemotherapies. This suggests that new cancer drugs could have dangerous side effects in the heart. The team also believes that Epac-Rap1 may be compromised in diabetes, which is a major risk factor for heart disease. In this BHF-funded programme, the Leeds research team will uncover exactly how Epac-Rap1 dampens the production of toxic molecules in healthy hearts. They’ll study how diabetes impairs this defence and how chemotherapies affect it to cause irregular heart rhythms. It is hoped that by understanding more about Epac-Rap1 we might find a way that new cancer therapy drugs can be used more safely at higher concentrations. In addition, understanding how Epac-Rap1 is affected by diabetes could lead to new treatments for associated heart problems.