New research suggests that a little-studied enzyme ACAT2, may play a major role in cardiovascular disease because it alters the molecular structure of cholesterol.
Artery-clogging plaque, which is produced from cholesterol in our diets can cause heart attacks and strokes and drugs which target that enzyme could dramatically reduce the risk of heart disease.
Lawrence Rudel, Ph.D., professor of pathology at Wake Forest University School of Medicine, says their research in animals shows that ACAT2, a cholesterol transforming enzyme, is a potential treatment target to protect people against heart disease.
According to the American Heart Association cholesterol is made by the liver and is also found in foods such as meat, fish and dairy products and 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 focussed 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 have shown 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. Rudel says that mice without ACAT2 do not get atherosclerosis.
Rudel and colleagues have confirmed their results in normal mice by using a molecule that blocks the effects of ACAT2, and will follow it with a pilot study in monkeys. He hopes the research will lead to a drug that can inhibit the enzyme’s production in humans, it is already known that humans produce ACAT2 and that women have lower levels than men.
Research has shown that estrogen can lower ACAT2 production, which may explain why women are less likely than men to get heart disease during their estrogen-producing years.