When researchers fed a high-fat diet to mice lacking the molecule beta3 integrin, they found the exact opposite of what they expected: The mice developed lung inflammation and clogged arteries and about two-thirds of them died within six weeks. The results suggest that long-term suppression of this molecule may exacerbate the development of heart disease, rather than prevent it.

The study will appear online the week of May 12 in the Proceedings of the National Academy of Sciences.

"We were amazed that these animals died from a high-fat diet," says the study's principal investigator Clay F. Semenkovich, M.D., professor of medicine and of cell biology and physiology and director of the Division of Endocrinology, Metabolism and Lipid Research. "This uncovers an interesting role for beta3 as a potential mediator of inflammation and may help guide new drug development strategies."

Beta3 sits on the surface of cells and interacts with other molecules in the body to help regulate functions like blood clotting and inflammation. Because one of the proteins it interacts with is critical for blood platelets to form clots, drugs that block the action of beta3 often are used to treat people who are having a heart attack. By inhibiting beta3, scientists believe these drugs prevent platelets from accumulating in blood vessels and help preserve normal blood flow.

In the past few years, many experts have hypothesized that long-term use of beta3 inhibitors may prevent arteries from clogging and thereby prevent heart attacks, which is the most common cause of death in the United States. Preventing heart disease is an exciting prospect considering that thousands of people die every year from a sudden ruptured plaque without having experi
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Contact: Gila Z. Reckess
reckessg@msnotes.wustl.edu
314-286-0109
Washington University School of Medicine
12-May-2003