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Study in Circulation provides detail on how low blood flow promotes vascular disease
Date:6/23/2008

sel walls. The current study unites the three discoveries by providing strong evidence that cyclophilin A, a protein involved in the immune response, has dual roles in vascular disease. It recruits immune cells that cause inflammation, and it drives pathogenic growth and remodeling, when triggered by reactive oxygen species in diseased blood vessels.

"For years researchers worldwide have sought to determine exactly how low blood flow and the immune reaction to cholesterol deposits, along with the reactive oxygen species created by both, drive the progression of atherosclerosis," said Bradford C. Berk, M.D., Ph.D., professor of Medicine in the Aab Cardiovascular Research Institute within the University of Rochester Medical Center, and senior author of the study. "We are tremendously excited by these results because they provide solid evidence that cyclophilin A is at the center of it all."

Study Details

The study results reflect blood vessel anatomy. Blood flows through the innermost part of a vessel called the lumen. The inside of that inner tube is lined with a layer of endothelial cells, which is surrounded by the fibrous cells of the intima, which is surrounded by a layer of smooth muscle cells in the media. Many blood vessels are muscular because the flexing of such muscle helps to control blood flow (blood pressure).

To examine the reaction of CyPA signaling to the overproduction of reactive oxygen species, Berk's team genetically engineered one group of mice to produce less CyPA, another group to make more, and compared both groups to "normal" mice as all three groups experienced reduced blood flow in the carotid artery. Reduced blood flow increased CyPA expression in the vascular wall, and promoted the migration of smooth muscle cells into the intima, where they began to grow (proliferate) and contribute to the formation of atherosclerotic lesions. Reduced flow, and the related increase in CyPA signaling, also c
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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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