Completed Heart, Stroke & Blood Cells, Biochemistry & Physiology

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

Funder MRC (part of UKRI)
Recipient organisation University of Manchester
Funding £1.3M
Period Jan 2012 — Jan 2017

In plain English

AI plain-English summary

Around 1 million people in the UK have heart failure, and their survival rates are similar to those for some cancers. A single gene—the plasma membrane calcium pump isoform 1 (PMCA1)—appears to be central to all three main causes of death in these patients: pump failure, dangerous heart rhythms, and high blood pressure. This matters because current treatments for heart failure are highly unsatisfactory. The PMCA1 gene works by moving calcium out of heart muscle cells, which helps the muscle relax and lowers blood pressure. Recent human genetic studies have already linked PMCA1 to disease, but exactly how it functions in the heart and blood vessels remains unknown. The researchers will study genetically modified mice to understand PMCA1’s role in detail. If this fundamental science succeeds, it could reveal a new target for drugs that address the root causes of heart failure and hypertension simultaneously—rather than just managing symptoms. That could change how millions of people are treated for a condition that is rapidly growing in prevalence.

View original technical description
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.

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Researchers

Clare Austin (Co-Investigator)Elizabeth Cartwright (Co-Investigator)Ludwig Neyses (Principal Investigator)Ming Lei (Co-Investigator)

Related Research

Grants with similar aims, by meaning.

Integrative Physiology of the Plasma Membrane Calcium Pump Isoform 4 in the Healthy and Failing Heart
The sarcolemmal calcium signalling protein PMCA4 as a novel target to reduce cardiac hypertrophy and failure
Modulation of calcium signalling in cardiac fibroblasts by the Plasma Membrane Calcium Pumps (PMCA) to improve pathological cardiac remodelling
Understanding the calcium uptake in cardiac sarcoplasmic reticulum: toward new routes to combat human dilated cardiomyopathy
Regulation of Ca(v)1.2 in cardiac health and disease

Original classification

Research Grant

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