The latest insight into hardening of the arteries could lead to novel drugs to prevent heart attacks and stroke.
Doctors are searching for new heart disease drugs
Experiments in mice suggest the disease can be stopped by targeting an enzyme found in the liver and gut.
The enzyme plays a critical role in the transport of cholesterol out of the liver into the blood.
Modified mice missing the gene did not develop hardening of the arteries (atherosclerosis) and had a much lower level of cholesterol in their blood, according to US scientists.
The gene codes for an enzyme called ACAT2 is found in the liver and the intestines.
Monkeys with high levels of the enzyme are known to be at greater risk of atherosclerosis.
Researchers think it may be possible to develop drugs to block the action of the enzyme and thus prevent the disease.
"Our results support the rationale of pharmacological inhibition of ACAT2 as a possible therapy for atherosclerosis," said co-researcher Dr Lawrence Rudel of Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina.
He says the next step is to look for drugs that inhibit the human version of the enzyme.
This could lead to a way to stop the body absorbing cholesterol after eating a high-fat meal.
The research is published in the Proceedings of the National Academy of Sciences.
ACAT 2, which stands for acylCoA:cholesterol acyltransferase 2, converts cholesterol into the form that accumulates on the inside of arteries.