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New Fungus Compounds Halt Hardening of Arteries

In study of mice, they prevent accumulation of blood fats

TUESDAY, Jan. 13, 2004 (HealthDayNews) -- Two compounds derived from a fungus and tested in mice seem to prevent the accumulation of lipids in cells where hardening of the arteries begins, a Japanese study finds.

If the research bears out, it could help scientists develop new drugs for treating atherosclerosis. The report appears in this week's issue of the Proceedings of the National Academy of Sciences.

In the early stages of atherosclerosis, which boosts the risk of heart attack and stroke, cells called macrophages store cholesterol and fatty acids, setting the stage for hardening of the arteries.

The Japanese team isolated the compounds from the Beauveria fungus and called them beauveriolides. They tested the activity of the compounds in macrophage cells and found the compounds stop the formation of lipid droplets and the activity of an enzyme called acyl-CoA:cholesterol acyltransferase (ACAT), thus preventing the cascade of events that eventually lead to hardening of the arteries.

When tested in mice bred to develop atherosclerosis, these compounds reduced the atherosclerotic lesion formation by about 50 percent in the treated mice, compared to controls. And they did so without causing side effects such as damage to adrenal tissue, which has been found with similar compounds used to inhibit ACAT.

"We first reported that beauveriolides inhibit lipid droplet accumulation in macrophages in 1999," says study author Hiroshi Tomoda, a professor at the Kitasato Institute for Life Sciences & Graduate School of Infection Control Sciences at Kitasato University in Tokyo.

In this study, the team showed the beauveriolides inhibit ACAT enzyme activity directly.

The study reports "an interesting and new finding of a novel compound," says Dr. Gregg Fonarow, a professor of cardiology and a researcher at the UCLA David Geffen School of Medicine in Los Angeles. Eventually, Fonarow says, the compounds may have a therapeutic use.

A variety of such inhibitors have been developed previously, Fonarow says, but when they were tested in small human clinical trials to assess safety some problems surfaced, including toxicity to adrenal tissue and other side effects.

The new compounds, Fonarow adds, "are significantly different. They target the macrophages specifically."

As exciting as the new discovery is, Fonarow notes, therapeutic use is probably five or 10 years away, and that's if the research bears out.

But he notes the statin drugs now commonly used to lower cholesterol were originally derived from fungal compounds, too.

Tomoda's team has already synthesized a number of the fungal compound derivatives and the researchers are searching for more. Hopefully, he says, there will be many such fungal derivatives to test for eventual use in humans.

More information

For more information on hardening of the arteries, see the American Heart Association or the National Library of Medicine.

SOURCES: Hiroshi Tomoda, professor, Kitasato Institute for Life Sciences & Graduate School of Infection Control Sciences, Kitasato University, Tokyo; Gregg Fonarow, M.D., professor, cardiology, and preventative cardiology researcher, UCLA David Geffen School of Medicine, Los Angeles; Jan. 12-16, 2004, Proceedings of the National Academy of Sciences
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