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Duke Researchers Genetically Engineer Mice To Block Heart Enlargement

time the heart walls can harden and hamper rather than bolster the pumping action. This leads to congestive heart failure.

Congestive heart failure is notoriously difficult to treat, although early symptoms are often mild, and can be treated with changes in diet and exercise. As the disease progresses, less and less can be done. Traditional treatments for the early stages of heart failure include drug regimens consisting of multiple medications, such as beta blockers and ACE-inhibitors, to block the various hormones that produce a strain on the heart. If these drugs fail and the disease progresses, patients can receive a heart transplant as a last resort.

"Right now patients with hypertension are treated with several drugs that block the action of various hormones," said Koch. "Now that we have shown Gq is the final common pathway that signals pressure overload hypertrophy, we think it will be possible to design a single drug or gene therapy strategy to do the work that many separate types of drugs accomplish now. We believe such a strategy may be more efficient, since such a drug would target a specific molecule (Gq) instead of only one of a multitude of receptor signals, which is the case now."

The researchers, which also include Dr. Shahab Akhter, the paper's first author, Dr. Louis Luttrell, Dr. Guido Iaccarino, Dr. Robert Lefkowitz, a Howard Hughes Medical Institute investigator, all of Duke, and Dr. Howard Rockman of the University of North Carolina at Chapel Hill, hope to develop strategies to treat congestive heart failure in people using gene therapy, insertion of genes into heart cells to prevent or repair damaged heart muscle. The research was supported by grants from the National Institutes of Health, a National Research Service Award, and the North Carolina chapter of the American Heart Association.

The hormones angiotensin II, endothelin I, a
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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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