For the first time, the breakdown product of lipid by the enzyme causes necrosis and heart failure. This finding can potentially lead to a new treatment for heart failure. More study is needed to know the significance at the clinical setting.
Kinya Otsu, Professor of Cardiology
13 September 2023
Discovery of heart cell mechanism holds promise for future heart failure treatments
Research into an enzyme involved in necrosis (uncontrolled cell death) has uncovered a new mechanism that could form the basis of new therapies against heart failure.
A biological mechanism in the heart’s muscle cells has been linked to one of the main causes of heart failure, opening up possibilities for future treatments.
As part of the study, which was published in Nature Communications, researchers removed a specific enzyme located in cardiac muscle cells from mice. Strikingly, the heart remained in good health despite the scientists creating situations that would normally cause dysfunction in the heart.
Further investigation was subsequently carried out on the enzyme, which is named iPLA2b. iPLA2b produces a lipid molecule called lysophosphatidylserine, which the researchers studied to look at how it binds to a receptor on the outside of the cardiac muscle cell, and the effect of this on the cell. When the presence of this receptor was reduced on cardiac cells in the laboratory, they found that there was less necrosis of these cells.
These results shine a light on a new mechanism within the body that can contribute to heart damage, especially when the heart is experiencing great amount of pressure. This mechanism could be an important target for future therapies.
Heart failure, where the heart does not work well due to one of various heart diseases, is a major cause of mortality in developed countries. Unless solutions are found, this trend will likely continue to grow as death from heart failure is disproportionately found in the elderly and many countries are experiencing shifting demographic towards ageing populations.
Modern treatments have improved the mortality rates for people who experience heart failure, but cases of the disease still remain high and the scientific community is focused on developing new therapies.
One cause of heart failure being investigated is the death of the heart’s muscle cells. Cells are always dying, and the body has a controlled method to kill cells. However, many cells will also experience an uncontrolled cell death (referred to as necrosis), and it remains a major cause of heart failure.
iPLA2b and lysophosphatidylserine are associated with necrosis of the cells, and this discovery holds potential as a basis for future treatments. However, their removal has also been linked to other health problems within mice, including progressive motor disorders and age-related neuropathology. Characterising it was a ‘double-edged sword’, the researchers argue that more work is required to understand this process and develop future therapies.
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BHF Professor of Cardiology