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Newly Discovered Role for Heart Response Enzyme May Yield Better Heart Failure Therapy

Duke University Medical Center researchers have identified a new protein that plays a critical role in enabling the heart to respond to such external stimuli as exercise or stress, as well as in the progressive loss of heart function that is heart failure, the researchers said.

Their findings, they said, suggest new approaches to prevent or reverse heart failure, which affects two to three million people in the U.S. The team reports its findings in the August 2005 issue of Nature Cell Biology. The study is now available as an advance online publication.

"We've uncovered new details of the first step of heart failure, in which heart receptors that normally allow the heart to adapt in the face of changing conditions are lost, rendering the heart unable to pump enough blood to meet the needs of the body's other organs," said cardiologist and geneticist Howard Rockman, M.D., of Duke. "If we could prevent this loss of heart receptors, we might improve heart function in patients with heart failure."

The enzyme the researchers studied, called phosphoinositide 3-kinase (PI(3)K), governs the function of beta-adrenergic receptors on the surface of heart cells. Such receptors are protein switches that nestle in the cell membrane and that are activated by the hormone adrenaline to enhance the heart's pumping action in response to exercise or stress.

In heart failure patients, chronic stress leads to an excess of adrenaline, over-stimulating beta-adrenergic receptors, a process that results in receptor desensitization and loss, Rockman said.

Earlier work by Rockman's team identified PI(3)K as being required for beta-adrenergic receptors to be drawn back into the cell for recycling once they have been activated. Those studies showed that increases in PI(3)K underlie the loss of beta-adrenergic receptors in animals and patients with heart failure, Rockman said.

The researchers' earlier experiments showed that disrupting the function o
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Source:Duke Health


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