Protective proteins in heart failure

Investigating a new endoplasmic reticulum-centred cardioprotection mechanism

Heart failure is a devastating condition which affects over half a million people in the UK, and there is currently no cure. Scientists are trying to find new ways to repair the damage to heart muscle using stem cells, or help the heart to work properly using implantable devices that can partially or completely replace the function of the failing heart. But we must also find out if we can protect the heart from further damage. Proteins that cells release or use within their outer surface play critical roles in heart health and disease. We know that a compartment of the cell called the endoplasmic reticulum (ER), where these proteins are made, folded and ‘checked’ for quality control, is vital for heart muscle cells to survive. In many forms of heart disease, the ER is not functioning properly. Dr Xin Wang and scientists at the University of Manchester have found that an enzyme named p21 activated kinase 2 (Pak2) is located within the ER and is crucial for its function. The BHF has now awarded them a grant to find out if and how Pak2 helps to maintain a healthy endoplasmic reticulum in heart muscle cells, preventing cells dying and ultimately helping the heart to work properly. This research will reveal if Pak2 could be a new target for drugs to slow and reduce the progression of heart damage to heart failure.