An enzyme responsible in increasing heart attack : New Study

North Carolina scientists identified a key enzyme in turning cholesterol into artery-clogging plaque, a finding integral to preventing atherosclerosis. New research suggests an enzyme called ACAT2 may be to blame for the build-up which is responsible for helping cholesterol leave the liver, where it is made, and travel to other parts of the body.

Many people think of cholesterol as a bad thing, but scientists are quick to point out the much maligned substance is actually needed to help insulate the nerves and keep cells healthy. Cholesterol is necessary for insulating nerves, making cell membranes and producing certain hormones. The body makes enough cholesterol on its own, however, so too much dietary cholesterol is a health risk, clogging the arteries increasing the possibility of a heart attack.

The problem is, too much of it ends up being warehoused inside the arteries, where it builds up as plaque and can cause heart attacks and strokes. It has not been clear, however, how cholesterol from food is transformed into the plague that clings to artery walls, causing atherosclerosis.

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.

ACAT2 is one of four enzymes responsible for helping cholesterol leave the liver, where it is made, and travel to other parts of the body. ACAT2 most often helps cholesterol travel to the arteries, where it builds up into the deadly plaque.

Investigators arrived at that finding after studying mice who were genetically altered not to produce ACAT2. Those mice had 85-percent less hardening of the arteries than mice who still produced the enzyme. When they gave normal mice a molecule known to block the effects of ACAT2, the same results were seen.

From there, they studied the enzyme in monkeys, looking specifically at whether certain foods might increase the effects of ACAT2 on cholesterol. So far the results are a little troubling. Monkeys who were fed diets high in monounsaturated fats like those contained in olive oil and nuts — so-called “goodâ€? fats — actually had the same rates of heart disease as monkeys who ate saturated, or so-called “badâ€? fats. Why? The researchers suspect monounsaturated fats, while reducing levels of “badâ€? cholesterol, are more susceptible to ACAT2.

The investigators believe these results and those of future studies may one day lead to a drug to target ACAT2 in humans, thus reducing the incidence of heart disease caused by plaque build-up in the arteries.

Rudel hopes the research will lead to a drug that can inhibit the enzyme’s production in humans. Scientists already know 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.

“All of these findings tell us that a potential treatment for protecting against heart disease is a compound that decreases ACAT2 activity,” said Rudel.

He said that one day, it may be considered important to test how much of patients’ cholesterol was altered by ACAT2, in addition to testing their levels of high-density lipoprotein (”good”) and low-density lipoprotein (”bad”) cholesterol.

“Reducing the risk of heart disease appears to involve more than affecting the levels of good or bad cholesterol,” said Rudel.