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

ts the properties of a susceptibility gene for hypertrophy," Olson said. "In principle we eventually could identify people who don't have enlarged hearts but have mutations in that gene and tell them they're at risk."

During the study Olson's team created mouse models that lacked HDAC9 and compared their heart development to that of normal mice. After one month under normal conditions, the hearts of the normal and HDAC9-negative mice were about the same size. But the hearts of the mice lacking the gene were, on average, 46 percent larger than normal by eight months of age.

Making the heart work harder than normal produced dramatic disparities.

The researchers first constricted the thoracic aortas in both the normal and HDAC9-negative mice to see how working harder to pump blood would affect heart growth. After three weeks, left-ventricle mass had increased by 56 percent in the normal mice and by 105 percent in mice missing the gene.

The researchers also artificially activated calcineurin in normal and HDAC9-negative mice. Four weeks later, heart mass in the normal mice had increased by 130 percent on average, compared to an average increase of 220 percent in the HDAC9-negative mice.

The research now will proceed on two fronts: The Donald W. Reynolds Cardiovascular Clinical Research Center at UT Southwestern eventually will screen participants in the Dallas Heart Study with enlarged hearts to see if they carry mutations in their HDAC9 genes as part of the center's effort to identify the set of genes involved in heart disease; and Myogen Inc., a Denver-based biotechnology company that Olson co-founded, has licensed the research in order to start investigating drug-development possibilities.

"Now that we know that HDAC9 is a key regulator of heart growth, we can use it to develop assays to find small molecules that could be developed into drugs," Olson said.


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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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