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Protein thought to protect against oxidative stress also promotes clogging of arteries
Date:1/10/2011

UCLA researchers have found that a protein that plays an important role in some antioxidant therapies may not be as effective due to additional mechanisms that cause it to promote atherosclerosis, or clogging of the arteries.

Published in the January issue of the journal Arteriosclerosis, Thrombosis and Vascular Biology, the finding may give clues as to why some antioxidant therapies have not yielded more positive results.

The protein, called Nrf2, has been thought to be an important drug-therapy target for diseases such as cancer because it can induce chemopreventive activity by attaching to specific sequences of DNA, leading to the release of numerous antioxidant and anti-inflammatory genes and enzymes that can decrease or inhibit the effects of carcinogens.

Researchers reasoned that Nrf2, with its potent ability to boost antioxidants, might also be useful in combating the cell and tissue damage, or oxidation, that leads to atherosclerosis.

However, UCLA scientists found that while Nrf2 boosted antioxidant properties in an animal model, it also increased the development of atherosclerosis by raising plasma cholesterol levels and cholesterol content in the liver.

According to researchers, this is the first study to document these additional effects on cholesterol metabolism in tandem with plaque formation in the arteries.

"We were very surprised at the finding," said principal investigator Dr. Jesus Araujo, director of environmental cardiology at the David Geffen School of Medicine at UCLA. "In fact, the atherosclerosis-producing factors were greater than the antioxidant benefits. The development of novel antioxidant therapies is quite important, and this research may help shed light on why treatments affecting this protein may not be as effective as we thought."

For the study, the team was able to isolate and identify Nrf2's actions by looking at what would happen in mice that w
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Contact: Rachel Champeau
rchampeau@mednet.ucla.edu
310-794-2270
University of California - Los Angeles
Source:Eurekalert

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