Medical Research Council - London Institute of Medical Sciences

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Energy Production Failure

Faulty energy production in heart cells precedes and may underlie heart failure – potential intervention target

11 March 2023

Energy Production Failure

The heart on the left is healthy but the one on the right exhibits the tell-tale signs of dilated cardiomyopathy, including overall enlargement, and thinning and weakening of the muscle walls. In most cases of such cardiomyopathy, the cause is unknown, but recent research indicates dysfunctional energy production, already known to accompany the condition, may actually be an underlying cause. Analysis of gene activity in heart tissue from patients with dilated cardiomyopathy and healthy controls showed expression of mitochondrial metabolism genes, especially two key transcription factors – KDM8 and TBX15 – was disrupted in patient samples. When scientists then deleted KDM8 in mouse hearts, they found the knock-on disruption of TBX15 and other metabolism genes preceded physical signs of cardiomyopathy by months. Knowing that impaired energy production can initiate rather than simply follow myocardial degeneration suggests maintaining it may be a way to slow or stop heart failure.

Written by Ruth Williams

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