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Research mice help scientists understand the complexities of cholesterol

Scientists at Wake Forest University School of Medicine and colleagues have developed new research mice to help them better understand how the body makes and uses "good" cholesterol to protect against heart attacks and strokes. Their latest findings are reported in the April issue of the Journal of Clinical Investigation.

"Being able to develop drugs to raise levels of good cholesterol depends on knowing more about the how and where the particles are formed," said John S. Parks, Ph.D., from Wake Forest University School of Medicine. "These animals provide the first tools to address these questions."

High-density lipoprotein (HDL) cholesterol is called "good" cholesterol because higher levels are associated with lower risk of heart attacks. Physicians and scientists believe that HDL carries cholesterol away from the blood vessels and to the liver, where it is passed from the body. It may also help remove excess cholesterol from plaque in arteries, slowing the buildup that can lead to heart attacks and strokes.

Parks, a professor of pathology in the Section on Lipid Sciences, is part of a multi-center team that has developed three groups of research mice to investigate the complexities of good cholesterol. These specially developed mice have mutations in a gene (ABCA1) involved in HDL production. The scientists are using them to pinpoint where good cholesterol is produced and how it helps fight plaque buildup. In one group of animals, the ABCA1 gene is selectively deleted in the liver which means their livers cannot produce HDL. It was through studying these mice that the scientists were able to report in 2005 that the liver is likely the body's main source of good cholesterol producing 70 to 80 percent.

Now, in the Journal of Clinical Investigation, they report that the intestines are the other source producing 20 to 30 percent. This finding came from studying mice with the ABCA1 gene deleted in the intestine. Before these findings,
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Contact: Karen Richardson
krchrdsn@wfubmc.edu
336-716-4453
Wake Forest University Baptist Medical Center
16-Mar-2006


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