"The plaques that clog arteries contain large amounts of fatty acids," says senior investigator Clay F. Semenkovich, MD. "We engineered mice that are unable to make fatty acid synthase in one of the major cell types that contribute to plaque formation. On a standard Western diet high in fat, the mice had less atherosclerosis than their normal littermates."
Animals can't survive without fatty acid synthase, so mice in this study were able to make the substance in most of their tissues. They couldn't manufacture it, however, in macrophages, a type of white blood cell that surrounds and kills invading microorganisms, removes dead cells from the body and stimulates the action of other immune cells. Macrophages are dispatched in response to injury, infection and inflammation.
Atherosclerosis is the most common cause of heart disease, which is the leading cause of death in the United States. Semenkovich, the Herbert S. Gasser Professor and chief of the Division of Endocrinology, Metabolism and Lipid Research, says doctors tend to concentrate on treating the surrounding risk factors related to atherosclerosis, such as diabetes and high blood pressure, but he says the blockages themselves cause the most serious, life-threatening problems.
"With the current epidemic of obesity and diabetes, people sometimes forget that it's the blockages in the arteries that really kill people," he says. "We've made progress using statin drugs, for example, that lower cholesterol and fight plaque buildup, but a lot of people who take statins still die from cardiovascular disease. We need better therapies."
These mouse experiments suggest targeting fatty acid synthase in macrophages may provide a potential treatment strategy for humans.
|Contact: Jim Dryden|
Washington University School of Medicine