The role of chemical messengers in heart failure

The role of abnormal local Ca2+ signalling in myocardial dysfunction induced by sustained β1- adrenoceptor activation or phosphodiesterase inhibition

During heart failure, changes in the heart reduce its ability to pump blood efficiently to the brain and body. One important change during heart failure is disruption to a critical process called calcium signalling. Calcium plays an important role in heart cells as a messenger. It is released from stores in response to chemical signals and helps each heart cell to contract in a timely way, forming a regular heartbeat. A key molecule that regulates calcium levels in the heart is called cAMP. This programme grant goes to a team led by Dr Derek Steele, at the University of Leeds, who are trying to understand the role of chemical imbalances in heart failure. In particular they are studying a chemical messenger called phosphodiesterase. During heart failure, a reduction in the amount of phosphodiesterase in the heart can alter cAMP levels, modifying calcium signalling. This may contribute to heart cell overgrowth and death. This team of researchers, using animal models and experiments looking at cells under a powerful microscope, aims to discover more about disruption to molecular signalling in the heart during heart failure. Their work will shed light on the important role played by phosphodiesterase on the levels of calcium in the heart. It is essential to understand these processes in order to develop new potential treatments for heart failure.