Scientists Identify Enzyme That Weakens the Heart

A study on mice has shown that an enzyme makes the heart prone to chronic cardiac insufficiency.

Published online in the Proceedings of the National Academy of Sciences, the study also found that the suppression of the same enzyme helps the heart remain strong despite increased stress.

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The research team-consisting of researchers from the Internal Medicine Clinic at Heidelberg University Hospital, the University of Texas Southwestern Medical Center at Dallas, and Gottingen University Hospital-say that a key molecule for cardiac hypertrophy brought on by stress is the naturally occurring enzyme CaMKII delta (Calcium/Calmodulin-dependent kinase II delta).

Dr. Johannes Backs, head of a research group, has revealed that his international team proved this in genetically modified mice that could no longer produce this enzyme by surgically obstructing the main aorta to put the heart under greater stress, and thus simulate permanent high blood pressure or valve stenosis in humans.

The researcher said that the anticipated enlargement of the heart was very slight - the animals were protected.

"With these mice, we succeeded for the first time in specifically suppressing the CaMKII delta enzyme and clarifying its function in detail," said Dr. Backs.

According to the researchers CaMKII delta has a direct effect on the cells' stress response, and if it is missing, certain information in cell DNA is not accessed that is normally activated by stress, leading to hypertrophy of the heart.

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"There was still some slight enlargement of the heart, but presumably not enough to cause cardiac insufficiency," said Dr. Backs.

Under normal conditions, the genetically modified mice were inconspicuous - their hearts functioned and reacted normally.

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Based on their observations, the researchers came to the conclusion that the function of CaMKII delta as an intermediate of the heart's stress response might be a possible approach for effective therapy.

They anticipate that agents that block only this function of the enzyme would prevent the heart muscle from reacting to overload.

Other functions of CaMKII delta should not be affected in order to avoid harmful side effects, they say.

Source-ANI
SRM