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Duke Researchers Genetically Engineer Mice To Block Heart Enlargement

DURHAM, N.C. - Researchers at Duke University Medical Center have genetically engineered mice to produce a protein that acts as a molecular decoy to stop enlargement of the heart -- a primary step to heart failure.

The decoy mimics a small portion of a protein called Gq, a molecular switch that causes heart cells to grow in response to high blood pressure. Flooding cells with non-working versions of Gq prevents the reception of molecular signals that normally would produce enlargement.

The research is the first to show definitively that Gq triggers enlargement of the heart, a common first step that leads to congestive heart failure, which kills 40,000 people a year in the United States.

The researchers -- who reported their research in the April 24 issue of the journal Science -- said their achievement raises the possibility that a single drug or genetic therapy could shut down the process that leads to enlarged heart in humans.

"We have shown in living animals that the final, common pathway to heart enlargement in response to pressure overload on the heart is through the protein Gq, which initiates the cascade of events inside the cell that lead to an enlarged heart," said Walter J. Koch, an assistant professor of experimental surgery, who led the team. "Our hope is that by demonstrating it is possible to block this initiation step, we will eventually be able to slow or prevent the steps that lead to heart failure in people."

Heart disease symptoms such as chronic high blood pressure and clogged coronary arteries put a strain on the heart. As it tries to compensate, the body produces hormones to force the heart to pump harder. This leads to an enlarged heart or myocardial hypertrophy. The heart gets bigger, it does not add any new muscle, and the existing muscle cells simply get larger. Although the additional muscle mass helps at first, over
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Contact: Karyn Hede George
Georg016@mc.duke.edu
919-684-4148
Duke University Medical Center
23-Apr-1998


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