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Mechanism of Heart Muscle Contraction Revealed

by Medindia Content Team on Apr 10 2008 5:33 PM

Two hitherto unknown enzymes play a key role in regulating the mechanism behind heart muscle contraction, a research team led by an Indian-origin researcher, has revealed.

Researchers at the University of Pittsburgh and the University of Chicago were able to control heart muscle function in a new way after uncovering the novel process.

The discovery, led by Pitt professor Sanjeev Shroff, the Gerald McGinnis Chair of Bioengineering in the Swanson School of Engineering, may pave the way for developing a less-taxing potential treatment for various heart diseases-including congestive heart failure.

The team was able to control heart muscle function in a new way after conducting experiments on slivers of heart muscle, which led them to disclose that heart muscle contractions can be regulated by the enzymes histone acetyltransferases (HATs) and histone deacetylases (HDACs).

It was found that acetylation of certain heart muscle proteins, i.e. a process wherein a radical cluster of atoms called an acetyl group attach to a protein and change its function, is facilitated by HATs and HDACs. While HATs trigger acetylation, HDACs remove the acetyl group rendering the muscle fibre more sensitive to calcium and subsequently leading to muscle contraction.

"This is a completely new process in the area of heart muscle contraction. Acetylation is widely known to regulate such events inside the cell nucleus as gene regulation, but it's never before been associated with heart muscle contraction," said Shroff.

Besides, they could intervene in this microscopic process to control heart muscle contraction, as they were able to inhibit HDACs, and increased the calcium sensitivity of the muscle fibers to strengthen contraction.

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According to Shroff, this could act as a possible treatment for such conditions as congestive heart failure and this technique could present an alternative to current therapies that fight heart muscle weakness by boosting cellular calcium content.

Though, the increased calcium level improves muscle contraction, it also causes more energy consumption in hearts that are already energy-starved.

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On the other hand, he added that HDAC inhibition alters a natural process to make heart muscle more sensitive to the existing calcium level.

"We did not create this process-we are just manipulating what is already there. The physiology to block HDAC is already there, and we just took advantage of that. This perturbation does not require greater mobilization of calcium, so we won't end up with increased cardiac energy consumption. That's been the Achilles heel of treatment so far," explained Shroff.

The study is published in a recent issue of the "Journal of Biological Chemistry."

Source-ANI
RAS/L


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