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Liver may be source of 'good' cholesterol

WINSTON-SALEM, N.C. Research in mice suggests that the liver may produce most of the body's "good" cholesterol, an unexpected finding that might one day help scientists develop new treatments to raise levels of this heart-protecting molecule in humans.

In the May issue of the Journal of Clinical Investigation, researchers from Wake Forest University School of Medicine and colleagues will report on a project that used gene-targeting in mice to simulate a rare disease in people Tangier disease. People with this genetic disease produce virtually no "good" cholesterol.

"In studies of mice, we provided the first definitive proof that the liver is the source of about 80 percent of the high-density lipoprotein (HDL), or 'good' cholesterol, that circulates in the blood," said John S. Parks, Ph.D., senior researcher, from the school of medicine, which is part of Wake Forest University Baptist Medical Center. "Understanding more about how HDL is produced could lead to new treatments to raise its levels."

Learning more about Tangier disease could help people with less severe cholesterol disorders, Parks said. Low levels of HDL are associated with higher risk of heart attacks, even when total cholesterol levels are normal.

People with Tangier disease have mutations in a gene (ABCA1) involved in the production of HDL. Like all genes, ABCA1 exerts its effects through a protein that it manufactures. The ABCA1 protein is found in many parts of the body, so scientists have been unsure which specific tissues are involved in HDL production. They suspected the liver played an important role because of high levels of ABCA1 there.

To test their hypothesis and learn more about how HDL is produced, the researchers developed mice without the ABCA1 gene in the liver which means their livers cannot produce HDL. The researchers measured HDL levels in these mice and found that concentrations of HDL were 80 percent lower than in normal mice. The mic
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Contact: Karen Richardson
krchrdsn@wfubmc.edu
336-716-4587
Wake Forest University Baptist Medical Center
8-Apr-2005


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