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Gene could hold key to predicting, combating life-threatening abnormal heart growth

DALLAS Aug. 23, 2002 Researchers at UT Southwestern Medical Center at Dallas have identified a gene they believe could predict risk for developing enlarged hearts and lead to treatments to control life-threatening heart growth.

In a study published in today's edition of Cell, a team led by Dr. Eric Olson, chairman of molecular biology at UT Southwestern, reports that the gene HDAC9 limits abnormal heart-muscle growth.

Olson said doctors have long understood that the heart becomes enlarged a condition called cardiac hypertrophy when it responds to stresses, including irregular heartbeat and high blood pressure.

Enlarged hearts frequently become dilated their inner chambers stretched beyond normal size and work less efficiently. The excess muscle also can disrupt the electrical signals that control heart rhythm. Cardiac hypertrophy frequently is a cause of sudden death among young athletes, who suffer cardiac arrest due to enlarged hearts without ever knowing they had the condition.

"Stress accelerates hypertrophic growth, and HDAC9 functions to restrict cardiac growth," said Olson. "If HDAC9 isn't present, it's like you have no brakes and the heart grows uncontrolled."

The new research also shows that HDAC9 specifically restricts cardiac growth in response to stress, but it does not restrict normal cardiac growth during development or in response to exercise.

Previous research had demonstrated that when the heart works harder than normal, a calcium sensor called calcineurin is activated and drives heart-muscle growth. The researchers showed that HDAC9 counteracts the calcineurin activity to short-circuit muscle growth.

While the gene doesn't completely stop heart enlargement, UT Southwestern researchers showed that HDAC9's presence significantly slows growth. Olson said the next step is to look at human subjects to see if abnormalities in HDAC9 coincide with abnormal heart growth.

"This gene exhibi
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Contact: Wayne Carter
Wayne.Carter@UTSouthwestern.edu
214-648-3404
UT Southwestern Medical Center
22-Aug-2002


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