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Gene may protect against heart disease rather than be harmful as previously thought

A genetic pathway whose activity was suspected to advance heart disease by increasing inflammation in the blood vessels and arteries feeding the heart may actually protect against it at least in laboratory mice, reports a team of Rockefeller University scientists led by Jan Breslow, M.D., in the Nov. 25 issue of Proceedings of the National Academy of Sciences.

The Rockefeller scientists' findings that blocking the NFkB pathway actually contributes to heart disease in the lab animals, occurred as part of their larger study to identify mechanisms of heart disease that are unrelated to one of the primary risk factors for the disease: high blood levels of "bad" cholesterol and low levels of "good" cholesterol.

"Having high cholesterol increases your risk, but does not mean that you will get heart disease," explains Susanne Idel, Ph.D., the Rockefeller scientist who is the lead author of the PNAS paper. "There are people who smoke, who are overweight, or who eat badly, and whose blood vessels and arteries don't become obstructed by the fatty build-up called plaques.

"So, there must be genetic pathways other than those connected to cholesterol metabolism. Our research has identified a non-cholesterol related gene that is linked to the development of heart disease in mice."

Understanding the actions of the NFkB (Nuclear Factor Kappa-B) pathway may suggest new treatment approaches against heart disease, the number one killer of adult men and women in the United States.

"Right now, the main ways we have to prevent heart disease relate to cholesterol, blood pressure and other risk factors for heart attack," says Idel. "In the long term, our hope is that we will have a more complex understanding of the genetics involved that gives us new tools for treating heart disease."

In the recent study, Idel, Breslow and co-author Hayes M. Dansky, M.D. (Cardiovascular Institute, Mt. Sinai School of Medicine) focused on the NFkB pathway and
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Contact: Joseph Bonner
bonnerj@rockefeller.edu
212-327-8998
Rockefeller University
26-Nov-2003


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