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Study in Nature Medicine establishes major new treatment target in diseased arteries
Date:5/10/2009

Removing a single protein prevents early damage in blood vessels from triggering a later-stage, frequently lethal complication of atherosclerosis, according to research published online today in the journal Nature Medicine. By eliminating the gene for a signaling protein called cyclophilin A (CypA) from a strain of mice, researchers were able to provide complete protection against abdominal aortic aneurysm (AAA).

The aorta is the main artery carrying blood from the heart, and AAA is a progressive outward dilation of the aorta under the stress of blood pressure due to a breakdown in the vessel's structural integrity. AAA leads to 15,000 deaths a year, mostly in aging men, when aneurysms rupture to spill blood into the abdomen, a fatal event in 90 percent of cases. Adding to the study's importance, AAA shares vital biochemical pathways with atherosclerosis, the leading cause of heart attack and stroke. Thus, drugs that target CypA could potentially address both AAA and atherosclerosis.

When study mice were engineered to remove their CypA gene, none from that group developed AAA in the face of the hypertension and high cholesterol known to accelerate it. In contrast, 78 percent of mice with "normal" amounts of CypA developed AAA under the same conditions, 35 percent with a fatal rupture. The team also found high CypA levels in the rupture-prone vessels of humans with AAA, and that major drugs like statins reduce CypA levels, which may partly explain their benefit.

"It is extremely unusual for the removal of one protein to provide absolute protection, but it makes perfect sense because cyclophilin A promotes three of the most destructive forces in blood vessels oxidative stress, inflammation and matrix degradation," said Bradford C. Berk, M.D., Ph.D., professor of Medicine within the Aab Cardiovascular Research Institute at the University of Rochester Medical Center, and senior author of the study. "We are working to design a
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Contact: Greg Williams
Greg_Williams@urmc.rochester.edu
585-273-1757
University of Rochester Medical Center
Source:Eurekalert

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