Fixing the volume switch in heart failure – targeting the control of noradrenaline release

Cyclic nucleotide coupled phosphodiesterase signalling in cardiac sympathetic neurons in heart disease: novel therapeutic targets

Injury to the heart muscle caused by a heart attack or high blood pressure can lead to heart failure, where it lacks the power to pump blood around the body efficiently. This is also associated with an increase in the release of a chemical (noradrenaline) from nerves, which makes the heart speed up when stressed. In healthy hearts, the release of a special messenger in these nerves can tell them not to release too much noradrenaline, a bit like turning down the volume switch. In diseased hearts this messenger no longer works so the volume is constantly high. Professor Paterson and his team have found a problem in the nerve cells of failing hearts that may reveal why the volume control breaks down. They discovered a defect in an enzyme called PDE2A, which means it can’t help to manufacture the chemical messenger that dampens down noradrenaline release. In this study they will try to target and fix the broken enzyme in nerve cells in the hearts of rats. They want to re-establish the normal signalling pathway that turns down the volume switch to prevent too much noradrenaline being released. If they can show it can be done, the fault in PDE2A could become a new target for the development of urgently need medicines for heart failure.