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Two drugs may stabilize plaques in atherosclerosis

WINSTON-SALEM, N.C. Two drugs that a Wake Forest University School of Medicine research team has been investigating for lupus for several years may stabilize atherosclerotic plaque in the walls of arteries and help avert heart attacks and strokes.

Nilamadhab Mishra, M.D., and colleagues reported at the American College of Rheumatology meeting in Washington that the two drugs TSA (trichostatin A) and SAHA (suberoylanilide hydroxamic acid ) decreased cholesterol deposits in the walls of arteries.

The two drugs are part of a class of drugs called histone deacetylase inhibitors, or HDIs, which work by multiple mechanisms, one of which is anti-inflammatory: they decreased inflammatory proteins produced by macrophages, a type of white blood cell. These inflammatory proteins can make the atherosclerotic plaque unstable. Mishra said. The macrophages were taken from normal mice and the experiments were done in a laboratory setting.

After the macrophages were treated with either TSA or SAHA, the researchers also measured dramatic decreases in LDL and total cholesterol in the macrophages.

And the drugs prevented macrophages from turning into foam cells inside arterial walls, which is a key component of the buildup of plaque that leads to a narrowing of the arteries and increases the risk of heart attacks and strokes.

With the growing understanding that atherosclerosis, also known as hardening of the arteries, is in part an inflammatory disease, Mishra noted that doctors might be able to take advantage of the anti-inflammatory effects of TSA and SAHA.

Mishra, a rheumatologist, is looking for new ways to treat atherosclerosis because, he said, "Premature accelerated atherosclerosis is one of the leading causes of death and disability in lupus."

He added, "There is great enthusiasm to develop drugs that can stabilize atherosclerotic plaque and reduce acute coronary events."

SAHA already is being tested as an anticancer drug, and TSA
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Contact: Robert Conn
rconn@wfubmc.edu
336-716-4587
Wake Forest University Baptist Medical Center
11-Nov-2006


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