| October 18, 2001
Combination of Vitamin E and Aspirin
Significantly Delays Atherosclerosis In Mice Even When
Cholesterol Levels Stay High
Penn Study Finds Plaque Production in Blood Vessels
Is Reduced More Than 80 Percent
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
"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
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,"
"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