(Philadelphia,
PA) - The original miracle drug, aspirin, continues
to surprise medical scientists. While studies have proven
that aspirin can prevent a second heart attack by thinning
the blood, researchers at the University of Pennsylvania
School of Medicine have shown that aspirin can also
prevent heart attacks and stroke through an entirely
different mechanism. Using laboratory models, the Penn
researchers demonstrated that aspirin also lessens the
inflammation associated with atherosclerosis and stabilizes
athersclerotic plaque. Their findings are presented
in the current issue of Circulation.
"The past decade has seen a lot of research indicating
that atherosclerosis is a chronic inflammatory disease,"
said Domenico Praticò, MD, assistant professor
in Penn's Department of Pharmacology. "Our findings
show that aspirin not only decreases inflammation in
the arteries and the growth of the atherosclerotic plaque,
but it also beneficially alters the consistency of the
plaque that remains."
Atherosclerosis, also known as hardening of the arteries,
is a main cause of heart attacks and strokes, two leading
causes of death in the United States. A variety of factors,
including genetics and diet, spur the disease, which
occurs as cholesterol-rich cells of the immune system
accumulate inside of blood vessels. As these plaques
grow, they cause the blood vessels to narrow. If a portion
of the plaque breaks off it can induce the formation
of a thrombus, a blood clot that could completely obstruct
blood flow and cause a heart attack. Likewise, a portion
of the thrombus could also travel through the bloodstream
to the brain, where it could cause a stroke.
The Penn researchers found that low-dose aspirin leads
to a change in the composition of the plaque, turning
it from a soft foamy material to a harder material that
is less likely to rupture.
"After aspirin, we find more collagen and smooth
muscle cells in arterial plaque and significantly less
cholesterol-rich cells," said Praticò. "Of
course, it is better to have no plaque at all, but if
you have plaque in your arteries, you would prefer it
to stay put - where it will do the least harm."
Although the exact causes of atherosclerosis are unclear,
researchers have known that the inflammation found in
atherosclerosis is associated with increased levels
of cellular inflammatory signals called cytokines. Plaque
formation is also associated with increased levels in
the aorta of a protein called NF-?B that controls the
formation of these cytokines, stimulates the growth
of immune cells and the accumulation of low-density
lipoproteins (LDL) - also known as the 'bad' cholesterol.
The Penn researchers have found that aspirin lowers
the amount of both cytokines in the blood stream and
the NF-?B in the aorta, suggesting a potent anti-inflammatory
action of the drug.
Praticò and his colleagues hypothesize that these
novel effects of low-dose of aspirin are independent
from its known function as blood thinner.
Aspirin directly inhibits the cycloxygenase (COX) enzyme,
which allows platelets in the blood to form clots. After
aspirin blocks COX, it enables this enzyme to produce
powerful anti-inflammatory molecules such as lipoxins,
which in turn could inhibit the formation of cytokines
- the very molecules that may stimulate atherosclerosis.
While Praticò recognizes more research needs
to be done, aspirin could provide a potent, and inexpensive
way to fight atherosclerosis. Low-dose aspirin has already
been proven effective in preventing a second heart attack.
There is a danger, however, taking large doses of aspirin,
which can lead to gastrointestinal bleeding.
So, what constitutes a low-dose?
"Generally, we consider between 80mg and 250mg
of aspirin to be 'low-dosages' - about the amount you
would find in children's aspirin," said Praticò.
"Of course, anyone considering taking a regimen
of low-dose aspirin should consult a physician first."
The research detailed in this study was supported by
grants from the American Heart Association and the National
Institutes of Health.
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Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.
The Perelman School of Medicine is consistently among the nation's top recipients of funding from the National Institutes of Health, with $550 million awarded in the 2022 fiscal year. Home to a proud history of “firsts” in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the mRNA technology used in COVID-19 vaccines.
The University of Pennsylvania Health System’s patient care facilities stretch from the Susquehanna River in Pennsylvania to the New Jersey shore. These include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Lancaster General Health, Penn Medicine Princeton Health, and Pennsylvania Hospital—the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.
Penn Medicine is an $11.1 billion enterprise powered by more than 49,000 talented faculty and staff.