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NIEHS-cloned gene linked to a natural substance that reduces vascular,,inflammation, a key to arterial clogging

Scientists at National Institute of Environmental Health Sciences, Brigham and Women's Hospital in Boston, and the University of Virginia have shown that naturally occurring fatty acids can help prevent vascular inflammation, a key component in the development of atherosclerosis-- the so-called "hardening" of the arteries that leads to many heart attacks and strokes.

The fatty acids are made by an enzyme produced by a gene first cloned at NIEHS -- and the gene itself, when implanted in the arterial cells, can produce the same protective effect, the researchers said.

The findings were published in the journal Science.

The fatty acid studies were performed in cultured human cells (from the lining of the arteries) and in live mice. They show that the introduction of fatty acid compounds called EETs can suppress the inflammation of arteries and may thereby protect against the development of atherosclerosis.

James Liao, M.D., of the Harvard-associated Brigham and Women's Hospital, said EETs may also be important in some cancers and rheumatic diseases where inflammatory cells have a role.

Darryl C. Zeldin, M.D., of NIEHS, a senior co-author on the study, originally cloned the CYP2J2 gene. "Since our studies have thus far been limited to tissue cultures and mice, we are still at a very early phase of discovery on the anti-inflammatory potential of the EETs and their stable analogs in humans," Zeldin said, "but the results show exciting potential."

Indeed, Liao said, "EETs may be the next generation of molecules that can be used to combat atherosclerosis and other diseases arising from inflammation." Atherosclerosis, a thickening and build-up of plaque in the arteries, occurs when the innermost layer of the artery, the endothelium, becomes damaged by cholesterol, toxins, oxidants, or infectious agents.

The damaged endothelial cells in the artery walls produce adhes
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Contact: Bill Grigg or Tom Hawkins
hawkins@niehs.nih.gov
919-541-1402
NIH/National Institute of Environmental Health Sciences
25-Aug-1999


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