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Published: Friday, 11/7/2003

Ozone linked to cholesterol-damaged arteries, researchers say

BY MIKE WOODS
BLADE SCIENCE EDITOR

Scientists today reported evidence that ozone - manufactured inside the human body - is a culprit in the artery-clogging damage that causes 1.1 million heart attacks in the United States each year.

Ozone is the gas famous as an upper-atmosphere guardian angel that shields Earth from ultraviolet rays and a nose-level villain involved in smog.

The toxic, acrid-smelling gas packs three oxygen atoms instead of the two found in regular oxygen. That gives ozone a powerful chemical punch, which can physically damage many materials.

An international research team discovered that tiny puffs of ozone are manufactured in cholesterol-laden deposits, or “plaques,” that plug arteries in the heart. Ozone then reacts with cholesterol in ways that encourage plaques to grow. It also may cause inflammation that further damages arteries.

“We are investigating what impact this discovery will have on other inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, and Alzheimer s disease,” Dr. Paul Wentworth, Jr., said.

Ozone, he suggested, could have previously unsuspected bodywide effects, acting as a signaling molecule. If so, it would join nitric oxide, another gas best-known as an air pollutant, in a growing family of gases that transmit messages and regulate body functions.

Dr. Ferid Murad and two associates who identified nitric oxide s role won a 1998 Nobel Prize, and the discoveries led to development of Viagra, the male impotence drug. Body cells also make carbon monoxide, a poisonous gas, and evidence suggests that it also is a messenger molecule.

“This is what our research is starting to show,” said Dr. Wentworth. “Ozone is going to be up there with NO and CO as biological signaling agents.”

In an interview from the University of Texas Medical School in Houston, Dr. Murad said he has been following the ozone research.

“I am not surprised that other gases may participate in cellular signaling and regulation,” he said. “Our early work with nitric oxide was just the beginning. I m sure more will be discovered.”

Dr. Wentworth and Dr. Richard Lerner, of the Scripps Research Institute in La Jolla, Calif., headed the research team, which included scientists from Switzerland and the United Kingdom. Their study results appear in the current edition of the journal Science.

Scientists have known for years that cholesterol does not act alone in forming plaques that narrow the inside of arteries like rust inside an iron pipe.

Something, for instance, chemically changes, or “oxidizes,” cholesterol so it can form plaques. Something inflames the plaques, causing further damage to the artery and inviting more cholesterol to settle.

Drs. Wentworth and Lerner used tests on surgical samples of diseased arteries to identify ozone as the culprit. They found that ozone is produced in plaques, probably by immune system cells that use it to help kill harmful microbes. The same cells, however, also concentrate in areas hit by inflammation.

“Production of ozone is a good thing because immune system cells can use it to destroy microbes,” Dr. Wentworth explained. “But it s a very bad thing in chronic inflammation,” he added, noting that ozone would fuel the process and increase tissue damage.

A blood test for the chemicals formed when cholesterol and ozone join forces, which are termed oxysterols, may become a new, noninvasive way of detecting artery disease, the researchers said.



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