A novel role for the plasma membrane calcium pump (PMCA1) in cardiomyopathy and blood pressure control

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Heart failure affects around 1 million people in the UK, patient numbers are rising rapidly and survival is similar to that of some cancers. Heart failure patients are known to die from two main causes, either pump failure or heartbeat abnormalities (arrhythmias). In addition, high blood pressure (hypertension) greatly aggravates heart failure. Improving treatment of heart failure, which currently is highly unsatisfactory, is the main motivation for our research. We have shown that a gene called the plasma membrane calcium pump isoform 1 (PMCA1) is central to all three key features of heart failure ? pump failure, arrhythmias and hypertension. By transporting calcium out of the cell PMCA1 helps the heart muscle to relax and blood pressure to fall. Strongly supporting our approach, recent genetic studies in humans have shown that PMCA1 is key to human disease. Our programme will take these findings to the next essential level, i.e. understanding the function of PMCA1. To this end we will study mouse models in which the level of PMCA1 in the heart and vessels has been genetically modified. This programme is pivotal for understanding heart failure and hypertension and will provide information essential to the development of new treatments.