Trichostatin A may fight lupus and atherosclerosis simultaneously

Nov 16 2005

People with lupus are prone to premature accelerated atherosclerosis. Now scientists at Wake Forest University School of Medicine think they have a way to prevent or decrease this atherosclerosis and prevent heart attacks.

"Premature accelerated atherosclerosis is one of the leading causes of death and disability in lupus," said Nilamadhab Mishra, M.D., a rheumatologist at Wake Forest University Baptist Medical Center. Using a drug called Trichostatin A (TSA) "may prevent or decrease premature atherosclerosis in lupus."

Mishra presented his findings at the American College of Rheumatology meeting in San Diego.

The findings represent a merger of two lines of Mishra's animal research using TSA – one showing that the drug reduced lupus symptoms, especially inflammation of the kidneys and enlarged spleens, and the other showing that TSA was effective against atherosclerosis.

Mishra was joined in the atherosclerosis research by several leading scientists in the Medical School's long-standing atherosclerosis research program.

Their research uses a mouse that was created to be prone to atherosclerosis when fed a diet high in cholesterol and with 10 percent of calories from palm oil, one of the more dangerous dietary vegetable fats since it is high in saturated fat.

Among the atherosclerosis researchers were John S. Parks, Ph.D., professor of comparative medicine, and Richard St. Clair, Ph.D., professor of pathology and head of the Section on Comparative Medicine.

For 12 weeks, the researchers fed a high-fat, high-cholesterol diet to two groups of the atherosclerosis-prone mice. One group got injections of TSA from the time they went on the diet, while the other group got no TSA. The TSA-treated group had markedly less atherosclerosis in key arteries, such as the aorta – the body's main blood vessel – and what plaque there was contained less cholesterol.

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

Mishra said that TSA may be beneficial because it prevents certain genes from expressing proteins that are known to be involved in both lupus and atherosclerosis.

Mishra had reported earlier that TSA showed promise in treating lupus in a different, lupus-prone mouse model. The research raises the hope, said Mishra, that "lupus and atherosclerosis can be treated simultaneously."