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Pulmonary hypertension in children may result from reduced activity of gene regulator
Date:3/5/2009

AUGUSTA, Ga. - Too little activity by gene regulators called PPARs appears to be a major player in the irreversible lung damage that can occur in children with heart defects, researchers say.

If they are right, drugs already under study to boost PPAR signaling in adults with lung injuries, may help these infants restore a healthy balance of blood vessel dilation and contraction, preventing the remodeling that transforms flexible blood vessels into rigid pipes and the pulmonary hypertension that often results.

"These drugs might be another therapy where you can treat some of the underlying mechanisms that have become deranged and reset the clock; essentially you can help the body go back to normal," said Dr. Stephen Black, a cell and molecular physiologist at the Medical College of Georgia's Vascular Biology Center.

About 1 percent of children are born with a heart defect with half requiring surgery. Improved surgical and medical treatments have improved survival rates for these children. Still their risk of related lung disease also can be deadly, researchers say as the high blood flow these defects produce pummels the lungs, turning flexible pulmonary blood vessels into rigid pipes, said Dr. Black, who co-directs the Cardiovascular Discovery Institute in the MCG School of Medicine.

Dr. Black and his colleague, Dr. Jeffrey Fineman, a whole-animal physiologist and physician at the University of California, San Francisco, want to understand the molecular mechanisms that disrupt regulatory mechanisms of the inner lining of blood vessels, or endothelium, and put children at increased risk. Dr. Black is principal investigator on two new National Institutes of Health grants and co-investigator on a third with Dr. Fineman to help dissect the dysregulation.

In a surgically created animal model of a congenital heart defect that causes too much pulmonary blood flow, they have already shown PPARs peroxisome proliferator-ac
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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
Source:Eurekalert  

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