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Penn scientists identify novel pathway in aneurysms

(Philadelphia, PA) Very little is known about how aortic aneurysms initially form and progress. Now, researchers from the University of Pennsylvania School of Medicine have shown in an atherosclerotic animal model that susceptibility for developing aneurysms increases significantly when an inflammation pathway important in asthma is activated. Mice without the inflammation gene were protected from aneurysms.

Colin D. Funk, PhD, former Professor of Pharmacology and Medicine, and Lei Zhao, MD, PhD, Research Associate, both in Penn's Center for Experimental Therapeutics, report their findings in this week's online publication and the September issue of Nature Medicine. Funk is now the Canada Research Chair in Molecular, Cellular and Physiological Medicine, Queen's University, Kingston, Canada.

"This is the first time anyone has ever shown aneurysm formation associated with this inflammation pathway," says Funk. Drugs that block the formation and action of this pathway are currently used to treat inflammation in the airways of asthmatics. "Perhaps they may become useful to treat patients who are susceptible to developing aortic aneurysms by blocking their progression and eventual rupture," he adds.

A gene for the 5-lipoxygenase-activating protein, which is required to synthesize leukotrienes, potent inflammatory molecules, has been associated with heart-disease risk. Leukotrienes, which constrict airways in asthmatics and contribute to inflammation in the lungs, are also associated with cardiovascular disease. They are secreted by inflammatory cells that gather at injured blood vessels.

Abdominal aortic aneurysms are a bulging region up to twice the normal diameter in the largest artery of the body. There is no known cure, with the only option of "watchful waiting" until surgical repair is attempted, says Funk. Often, but not always, these types of aneurysms are associated with arteriosclerosis, a chronic inflammatory disease of the
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-662-2560
University of Pennsylvania School of Medicine
22-Aug-2004


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