October 2001

From University of Pennsylvania Medical Center

Vitamin E and aspirin delay heart disease in mice even with high cholesterol levels

Penn study finds plaque production in blood vessels is reduced more than 80 percent

A combination of the anti-oxidant Vitamin E and a cox inhibitor such as aspirin significantly delays the development of atherosclerosis in mice even when their cholesterol levels remain high, according to research by scientists at the University of Pennsylvania School of Medicine.

In the study, the production of plaque in the blood vessels of the mice was lowered more than 80 percent, said Domenico Pratico, MD, research assistant professor in Penn's Department of Pharmacology and the lead investigator in the research. The findings are published this week in Circulation, a journal of the American Heart Association.

"We think this is a therapy regimen suitable for clinical trials," Pratico said. "The implication is that if you combine an antioxidant with even a low dose of aspirin, you might be able to obtain primary prevention of atherosclerosis without reducing cholesterol. This is something that might be used by individuals who cannot take cholesterol-reducing medication, and it would be a very inexpensive way to prevent such a deadly disease."

Pratico and his colleagues used a group of mice that had been genetically engineered to produce high cholesterol and atherosclerotic lesions similar to human plaques, in a series of studies that examined how the mammals' cardiovascular systems would respond to Vitamin E and aspirin or similar drugs when they developed the disease.

The first test group was administered a daily dose of Vitamin E that would have equaled 800 units in human subjects. "We found that Vitamin E reduced oxidative stress, which is known to be increased in atherosclerosis, to the point that it was suppressed in the mice," Pratico said. "It also reduced atherosclerosis by 65 percent. And this was accomplished without lowering the cholesterol levels."

When the second test group was administered the same dose of Vitamin E along with a dose of indomethacin that would have equalled 25 milligrams in humans, the results were even more compelling: "We found the synergistic effect from Vitamin E and indomethacin resulted in an 85 percent reduction of atherosclerosis," Pratico said.

"Atherosclersis is a complex disease, and high cholesterol is one of the many factors involved in its pathogenesis. Oxidative stress and inflammation are probably as important as cholesterol, if we can delay or prevent its onset with this combination of drugs," Pratico said. "We now have a scientific basis for evaluating in humans this unexpected therapy in the prevention of such a common and expensive disease."

The work was funded by the National Institutes of Health and the American Heart Association.

Pratico's collaborators in the research included: Tillman Cyrus, MD; Lina X. Tang, B.Sc., and Garret FitzGerald, MD, all of Penn's Center for Experimental Therapeutics, and Joshua Rokach, PhD, of the Claude Pepper Institute of the Florida Institute of Technology in Melbourne, FLA.











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