Nilamadhab Mishra, M.D., of Wake Forest University Baptist Medical Center, said the drug, called Trichostatin A or TSA, "may have a therapeutic benefit in atherosclerosis," which causes coronary artery disease by blocking key arteries, leading to death and disability. Mishra, assistant professor of internal medicine rheumatology, and his colleagues tested TSA on experimental mice that were bred to lack a significant natural protection against atherosclerosis. For 12 weeks, these mice were fed a diet that was both high in cholesterol and in which 10 percent of calories came from palm oil, one of the vegetable oils most likely to cause atherosclerosis. In addition to the coronary arteries, atherosclerosis also occurred in the aortic arch, part of one of the body's main blood vessels.

When Mishra compared the mice given TSA with mice given an inert substance, the amount of atherosclerosis deposited in the aortic arch was cut in half.

The TSA-treated mice also had a reduction in total and free cholesterol levels in the abdominal aorta, the lower portion of the aorta, the body's largest blood vessel.

These mice had a three-fold reduction in the gathering of macrophages, a type of white blood cell. Scientists increasingly are viewing the depositing of cholesterol in the walls of arteries as an inflammatory reaction that attracts the disease-fighting macrophages, which then become incorporated with cholesterol deposits to become plaque.

"The recognition of atherosclerosis as an inflammatory disease raised the question of whether anti-inflammatory drugs might decrease this disease process," said Mishra, who no
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Contact: Robert Conn
rconn@wfubmc.edu
336-716-4587
Wake Forest University Baptist Medical Center
18-Oct-2004