DALLAS -- April 17, 1998 -- Using two drugs already available, researchers at UT Southwestern Medical Center at Dallas may have found a cure for a condition that puts 5 million Americans at risk for sudden death -- an enlarged heart, or cardiac hypertrophy.

In groundbreaking research Dr. Eric Olson, chairman of molecular biology and oncology, and his colleagues discovered a molecular pathway that leads to heart enlargement and have found a way to block that pathway using an immunosuppressant drug already approved by the Food and Drug Administration, although not for that condition. Their study, published in the April 17 issue of Cell, was done in mice whose progression from cardiac hypertrophy to heart failure to death mirrored humans'.

"Cardiac hypertrophy is the response of the heart to all sorts of damage, like hypertension or heart attacks or endocrine disorders or mutations. What the heart does is try to compensate for that damage by increasing its size to achieve greater cardiac output," said Olson.

Initially this is beneficial, but ultimately the heart may enlarge too much, causing congestive heart failure that can lead to sudden death. Half of cardiac hypertrophy patients die from the condition.

Olson and his research team showed that cardiac hypertrophy is controlled by a single protein, calcineurin, which acts as a gatekeeper to the cells nucleus, the control room where specific molecules regulate gene function. When stimulated by a sustained increase in the cells calcium level, calcineurin activates its target protein, NFAT3, which then enters the nucleus and turns on the genes that cause heart enlargement.

The researchers genetically engineered two strains of mice to test their hypotheses. One strain continually expressed activated calcineurin in heart muscle cells, which allowed activated NFAT3 to enter the nucleus and start the hyper
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Contact: Heather Stieglitz
heather.stieglitz@email.swmed.edu
(214) 648-3404
UT Southwestern Medical Center
17-Apr-1998