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Protein implicated in decline of aging hearts

DURHAM, N.C. Duke University Medical Center researchers have linked elevated levels of a specific heart protein in elderly hearts to a decrease in the pumping ability of the heart.

Since levels of this protein, known as G-alpha-i, are also elevated in patients with congestive heart failure, the researchers believe that not only do they better understand why the heart's pumping ability decreases with age, but that there may be a pharmacological approach to prevent this age-related decline.

It is known that a class of drugs known as beta-blockers can improve the symptoms of patients with congestive heart failure. Interestingly, these drugs also reduce the levels of G-alpha-i, leading the researchers to speculate that beta-blockers drugs could be potentially used in healthy patients to forestall the natural decline of the aging heart.

The results of the Duke study were published today (Oct. 4, 2003) in the Journal of Cardiovascular Pharmacology. The study was support by the National Institutes of Aging.

G-alpha-i mediates signaling through a family of G protein-coupled receptors (GPCR), which are important in cardiac function. Beta-adrenergic receptors (beta-AR), which respond to the hormones epinephrine and norepinephrine in the so-called "fight-or-flight" response to increase cardiac output, are also members of this family.

G-alpha-i is one protein that can prevent these hormones from "coupling" to beta-ARs, thereby decreasing the heart's contractability. The mechanism of action for G-alpha-i appears to be its ability to block adenylel cyclase, an enzyme that resides within cells and is responsible for transmitting messages within the cell in response to hormonal stimulation.

"The results from our study suggest that the dampening of G-alpha-i activity in the human heart may improve the age-induced decreases in cardiac function," said Duke pharmocologist Madan Kwatra, Ph.D., principal investigator of the study. "From wh
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Contact: Richard Merritt
merri006@mc.duke.edu
919-684-4148
Duke University Medical Center
4-Oct-2003


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