The heart is an amazingly adaptable organ, responding to the needs of the organism throughout life, such as through periods of increased demand by pumping harder, faster, and also growing to accommodate longer-term requirements such as that experienced in pregnancy or as a response to intense exercise.
Some cardiac diseases, such as prolonged high blood pressure and heart attacks, also cause an increase in the heart’s muscle mass but dangerously this results in a reduction in cardiac output and can cause an irregular heart rhythm. This growth is called pathological cardiac hypertrophy and eventually leads to heart failure and death. Cardiovascular diseases account for a third of all deaths in the UK.
Now, researchers at the Babraham Institute (UK), KU Leuven, the University of Oslo, and the Karolinska Institute have uncovered the molecular control mechanisms responsible for the different biological changes seen in cardiac hypertrophy induced by pathology compared to exercise. These findings point the way for the design of new treatments for heart disease.
The research also analysed human cardiomyocytes and importantly the same molecular changes were seen, demonstrating that the same epigenetic factors underlie cardiac hypertrophy and disease remodelling in humans.
Professor Llewelyn Roderick, former group leader at the Babraham Institute, now Professor in the Department of Cardiovascular Sciences at KU Leuven, commented: “Our research has defined a novel epigenetic-based mechanism which explains the contrasting outcomes of cardiac remodelling caused by exercise and pathology. By identifying the epigenetic determinants and the responsible epigenetic enzymes controlling these different forms of cardiac myocyte hypertrophy, as well as how the epigenetic modifiers are themselves regulated by micoRNAs, we provide a potential strategy for epigenetic therapy for adverse cardiac remodelling. This work highlights the value of collaborative research to allow analysis from physiology to molecule and back again.”