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Eliminating enzyme dramatically reduces cardiovascular disease

WINSTON-SALEM, N.C. How does cholesterol in our diets end up as artery-clogging plaque that can cause heart attacks and strokes? Research in animals suggests that a little-studied enzyme may play a major role and that drugs to target it could dramatically reduce the risk of cardiovascular disease.

Lawrence Rudel, Ph.D., from Wake Forest University School of Medicine, presented new results from his research on ACAT2, a cholesterol transforming enzyme, today at the American Heart Association's Sixth Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology in Washington, D.C.

"Our research in animals tells us that ACAT2 is a potential treatment target to protect people against heart disease," said Rudel, a professor of and pathology (comparative medicine) at the School of Medicine, which is part of Wake Forest University Baptist Medical Center.

Cholesterol is made by the liver and also supplied through such foods as meat, fish and dairy products. According to the American Heart Association, cholesterol is needed to insulate nerves, make cell membranes and produce certain hormones. However, because the body makes enough cholesterol on its own, too much dietary cholesterol is associated with an increased risk of heart disease.

Rudel's work focuses on an enzyme that alters the molecular structure of cholesterol so that it can be transported to the body's cells. There are three different enzymes (ACAT1, ACAT2 and LCAT) that can change cholesterol into a form that can be more easily carried in blood.

Studies in both mice and monkeys show that cholesterol altered by ACAT2 is more likely to build up in blood vessel walls and cause atherosclerosis. In studies of genetically altered mice that do not produce ACAT2, levels of atherosclerosis are 85 percent lower than animals producing ACAT2.

"Mice without ACAT2 don't get atherosclerosis," said Rudel.

Recently, Rudel and colleagues confirmed these results in
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Contact: Karen Richardson
krchrdsn@wfubmc.edu
336-716-4587
Wake Forest University Baptist Medical Center
28-Apr-2005


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