Science
Detailed map of the heart provides new insights into heart health and disease
Researchers have produced the most detailed and comprehensive Human Heart Cell Atlas to date including mapping of the specialised cells responsible for the coordinated electrical activation of the heart, which allow it to beat. The results of the study, part-funded by us and the German Centre for Cardiovascular Research (DZHK), have just been published in the journal Nature.
The multi-centre team led by the Wellcome Sanger Institute and the National Heart and Lung Institute at Imperial College London is part of the international Human Cell Atlas (HCA) initiative, which aims to map every cell type in the human body to transform our understanding of health and disease.
Charting the heart’s wiring
Charting eight regions of the human heart, the work describes 75 different cell states, including the cells of the cardiac conduction system, which had never been profiled at single-cell level in humans.
The human cardiac conduction system and the cells that compose it, the heart’s ‘wiring’, sends electrical impulses from the top to the bottom of the heart and coordinates the heartbeat.
The new map acts as a molecular guidebook, showing what healthy cells look like, and provides a crucial reference to understand how cells become dysfunctional in disease. The findings will serve as a reference for disease studies, including conditions affecting heart rhythm, also known arrhythmias, of which atrial fibrillation is the most common and estimated to affect around 0.5% of the population worldwide.
Understanding the biology of the cells of the conduction system and how they differ from heart muscle cells paves the way to therapies to boost cardiac health and develop targeted treatments for arrhythmias.
Spotting warning signs
The study unearthed an unexpected discovery: a close relationship between conduction system cells and glial cells. Glial cells are part of the nervous system, including the brain, and have not been well studied in the heart.
This study suggests that glial cells are in physical contact with conduction system cells and may play an important supporting role by communicating with pacemaker cells, guiding nerve endings to them, and supporting their release of glutamate, a signalling molecule that helps control heart rate.
The researchers also identified cells within the heart that secrete Brain Natriuretic Peptide (BNP) a hormone that is used by doctors as a biomarker predicting someone’s susceptibility to heart failure. Their work shows that even in healthy hearts, a small population of muscle cells produces this substance.
By comparing this information with publicly available data from heart failure patients, the team found that these same cells grow in number in failing hearts. This opens the door to new therapeutic opportunities to prevent disease progression by targeting specific cell types.
“International collaboration is key”
Dr Michela Noseda, Senior Lecturer in Cardiac Molecular Pathology at the National Heart and Lung Institute, Imperial College London, who led the research, said: “We often don’t fully know what impact a new treatment will have on the heart and its electrical impulses – this can mean a drug is withdrawn or fails to make it to the market.
“Our team developed the Drug2cell platform to improve how we evaluate new treatments and how they can affect our hearts, and potentially other tissues too. This could provide us with an invaluable tool to identify new drugs which target specific cells, as well as help to predict any potential side-effects early on in drug development.”
Professor Metin Avkiran, our Associate Medical Director, said: “Using cutting-edge technologies, this research provides further intricate detail about the cells that make up specialised regions of the human heart and how those cells communicate with each other. The new findings on the heart’s electrical conduction system and its regulation are likely to open up new approaches to preventing and treating rhythm disturbances that can impair the heart’s function and may even become life-threatening.”
“International collaboration is key to scientific progress. This impactful study and other discoveries from the broader Human Cell Atlas initiative are excellent examples of what can be achieved when the international research community works together across borders. Our combined efforts can ultimately produce better outcomes for patients worldwide.”