399 South 34th Street
Suite 2002 Penn Tower

Philadelphia, PA 19104

Phone: (215) 662-2560
Fax: (215) 349-8312

Media Contact
(for this release only)

Karen Kreeger
(215) 349-5658


Current News

Press Releases

Publications

Events & Calendars

August 22, 2004

Penn Scientists Identify Novel Pathway in Aneurysms
Possible Implications for Some Anti-Inflammatory Drugs Used in Fighting Cardiovascular Disease

(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. (Click on thumbnail to view full-size image). 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 blood-vessel wall, consisting of fatty deposits that progress into major plaques that eventually break off from the inner lining and lead to heart attacks. “The danger of aneurysms is that we don’t normally carry out routine screening for their detection and by the time they are found most of the progressive damage may have already occurred,” explains Funk.

“This is a surprising finding since at first we weren’t even looking for aneurysms, we were trying to confirm the arteriosclerosis-leukotriene connection,” comments Zhao. The researchers found the 5-lipoxygenase enzyme mainly in macrophages in the outer layer of blood vessels not in the fatty atherosclerotic lesions of the inner layer, as expected. (Macrophages engulf such foreign objects as cellular debris, excess fats, and dying cells.) When the researchers inactivated the gene in a mouse model of arteriosclerosis, the number and degree of severity of aneurysms in the mice was markedly reduced. “In humans it has been very difficult to characterize the mechanisms for aneurysm formation and progression,” says Funk. “Often, studies have only revolved around pathological specimens obtained at autopsy or at the time of surgery.”

They concluded that leukotrienes derived from 5-lipoxygenase are one important clue in the progression of aneurysms but not in early atherosclerosis. More studies will be required in other models of aneurysm formation and in larger animals using currently available 5-lipoxygenase blockers before testing can begin in humans, say the researchers.

Penn colleagues on the paper are: Daniel J. Rader, Fredérique Pédrono, and Jinjin Fan. This research was funded in part by the National Institutes of Health and the American Heart Association.

For a printer friendly version of this release, click here.

###

PENN Medicine is a $2.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and high-quality patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System (created in 1993 as the nation’s first integrated academic health system).

Penn’s School of Medicine is ranked #3 in the nation for receipt of NIH research funds; and ranked #4 in the nation in U.S. News & World Report’s most recent ranking of top research-oriented medical schools. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

Penn Health System is comprised of: its flagship hospital, the Hospital of the University of Pennsylvania, consistently rated one of the nation’s “Honor Roll” hospitals by U.S. News & World Report; Pennsylvania Hospital, the nation's first hospital; Presbyterian Medical Center; a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home health care and hospice.

Privacy Policy Disclaimer Terms of Use