Steps on Enlarged Heart ‘Uncovered’

Researchers in the US claim to have got new insight into the mechanisms that underlie an enlarged heart — a finding that could lead to development of new treatment for managing this common cardiac ailment.

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An enlarged heart can lead to heart failure (Image: CNRI, Science Photo Library)

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According to them, high blood pressure, heart valve disease and heart attacks can lead to a abnormal thickening of the heart muscle, called myocardial hypertrophy, which plays a role in the pathological increase in the heart size.

At the molecular level, signals driving myocardial hypertrophy, like elevated levels of catecholamine hormones, activate the Myocyte Enhancer Factor (MEF) proteins. This alters gene expression in heart muscle cells and induces an adverse developmental paradigm known as “fetal gene response”.

“Previous research has shown that the signalling pathways leading to MEF2 are altered during pathological cardiac hypertrophy. Although we know that enzymes called histone deacetylases (HDACs) control MEF2 activity, it was not clear that HDACs and MEF2 were integrated into a larger signalling unit,” lead author John D Scott said.

To further identify the molecular mechanisms associated with cardiac hypertrophy, Scott and colleagues at the University of Washington studied cardiac A-Kinase Anchoring Proteins (AKAPs), which are known to play a critical role in organising signalling complexes in response to catecholamine hormones and transmitted signals within cells.

The researchers found that AKAP-Lbc functions as a scaffolding protein that selectively directs catecholamine signals to the transcriptional machinery to potentiate the hypertrophic response, the ‘Cell Press‘ journal reported.

“Our study supports a model where AKAP-Lbc facilitates activation of protein kinase D, which in turn phosphorylates the histone deacetylase HDAC5 to promote its export from the nucleus. The reduction in nuclear HDAC5 favoured MEF2 transcription and onset of cardiac hypertrophy,” Scott said.

Sources: The Times Of India

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