New Studies Impacting Deadly Atherosclerosis Have
Potential to Save Millions of Lives
Blocking ROCK1 could slow the disease; cooling the
inflammation; repair with artificial veins and arteries
Atherosclerotic lesion with and without ROCK1.
Click photo for larger view.
Courtesy of James K. Liao, M.D., Harvard Medical
School
June 18, 2008 - Even if you eat right and exercise
regularly, chances are high that you'll still die of a heart attack or
stroke. But thanks to new findings by researchers from Harvard and
Baylor, the odds may finally shift in your favor. Two studies published
online in The FASEB Journal describe findings on atherosclerosis that
have the potential to save millions of lives. A third reports on the
potential of repairing the damage using artificial.
The first two studies involved experiments in mice,
but cover biological processes present in humans.
In the first, scientists from Harvard explain how
the absence of a single protein, called "ROCK1," profoundly reduces
inflammation in the walls of blood vessels provoked by fatty deposits
(atherosclerosis).
In this study, scientists found that ROCK1 is
necessary for immune cells, called macrophages, to "clean up" vascular
walls when they come into contact with fatty deposits.
Inflammation is a normal byproduct of the clean-up
process and, when it goes unchecked, leads to clogging and hardening of
the arteries. When ROCK1 is absent, macrophages no longer contributed to
these fatty deposits and mice showed significantly less inflammation and
atherosclerosis.
This discovery could lead to new treatments, such
as ROCK1 inhibitors, that could dampen the inflammatory response to
fatty deposits and slow the progression of atherosclerosis, and in so
doing, reduce the incidence of heart attacks and strokes.
According to James Liao, MD, Director of Vascular
Medicine Research, Brigham and Women's Hospital, Harvard Medical School,
and one of the report's co-authors, "the ultimate goal of the research
is to prevent or slow atherosclerosis, and these findings provide a new
target to do this."
Cooling down the inflammation
While the first study works to prevent inflammation
by keeping cells of the immune system at bay, the second report focuses
on the body's ability (or inability) to "cool down" inflammation after
this clean-up machinery kicks into high gear.
When a person develops a sore or a boil, it erupts,
drawing to it immune system cells that fight the infection. Then it
resolves and flattens into the skin, often leaving behind a mark or a
scar.
A similar scenario plays out in the blood vessels. However, when there
is a defect in the resolution response – the ability of blood vessels to
recover from inflammation – atherosclerosis or hardening of the arteries
can result.
Separate researchers from Harvard, Brigham and
Women's Hospital and Baylor looked at how we prevent inflammation from
running amok. The scientists identified lipid mediators that the body
uses to resolve inflammation once it has started. By targeting these
lipid mediators and the mechanisms used to make them, scientists should
be able to develop drugs that significantly reduce the inflammation that
underlies much of atherosclerosis.
"The specific chemical mediators that naturally
cool down the inflammatory process identified in this study represent a
new drug target for anti-atherosclerosis therapy," said Aksam Merched,
PhD, Assistant Professor at Baylor College of Medicine and the first
author of the study.
"It's also noteworthy that aspirin stimulates the
body to produce one class of these chemicals."
"Even if we delay the process by exercise and
rabbit food, sooner or later our blood vessels rot," said Gerald
Weissmann, MD, Editor-in-Chief of The FASEB Journal.
"Now that we appreciate that atherosclerosis is
inflammation gone awry, we can attack its root causes. Studies like
these take us closer to delaying the inevitable, and help us understand
the factors that provoke heart attacks and strokes."
Third study finds new approach to repairing
damage
And as the first study aims to prevent
atherosclerosis before the immune system kicks into gear and the second
aims to prevent it after the immune system is activated, a third study
appearing on the cover of the June 2008 print issue of The FASEB Journal
discusses a new approach toward repairing the damage using artificial
grafts that may heal into the natural arteries and blood vessels as time
goes on.
A team of London scientists have taken a major step
in making the use of artificial veins and arteries in coronary bypass
grafts a reality. The researchers describe how they developed this
artificial graft tissue by combining man-made materials with human cells
to make it elastic and durable and so it can attach to host tissue
“Obviously this advance could be a medical
breakthrough that saves millions of lives around the world,” said Gerald
Weissmann, M.D., Editor-in-Chief of The FASEB Journal, “but even
more tantalizing is the successful fusing of living cells to nonliving
substances that actually—heal—by forming a stronger bond to each other
and to host tissue once put in use. This might even be called a start
toward ‘cyborg engineering.’”
In the research report, scientists describe how
they took an elastic scaffold (the material that gives the artificial
graft its shape) of compliant poly(carbonate-urea)urethane and
incorporated human vascular smooth muscle cells and epithelial cells
from umbilical cords.
Then they took the artificial grafts and simulated
blood flow in the laboratory to test their durability. They found that
as the pulsing fluid flow slowly increased, the artificial graft’s
performance actually improved. The researchers hypothesize that this
improvement is because the movement of fluid through the graft
stimulates the smooth muscle and epithelial cells to release proteins
that strengthen their ability to attachment to the elastic scaffold and
other tissues.
“The notion that any body part could be engineered
in a lab, attach to existing tissue ‘naturally,’ and grow stronger as it
is being used is something thought completely impossible just 20 years
ago,” Weissmann added. “It is only a matter of time before human tissues
can be engineered to be at least as good as the originals, and this
study moves us toward that reality.”
Helpful Information to Better Understand
Atherosclerosis and Its Consequences
Atherosclerosis
Atherosclerosis
is a type of arteriosclerosis. The name comes from the Greek
words athero (meaning gruel or paste) and sclerosis
(hardness). It's the term for the process of fatty
substances, cholesterol, cellular waste products, calcium
and fibrin (a clotting material in the blood) building up in
the inner lining of an artery. The buildup that results is
called plaque.
Arteriosclerosis is a general term for
the thickening and hardening of arteries. Some hardening of
arteries normally occurs when people grow older.
Plaque may partially or totally block
the blood's flow through an artery. Two things that can
happen where plaque occurs are:
● There may be bleeding (hemorrhage) into the plaque.
● A blood clot (thrombus) may form on the plaque's
surface.
If either of these occurs and blocks
the whole artery, a heart attack or stroke may result.
Atherosclerosis affects large and
medium-sized arteries. The type of artery and where the
plaque develops varies with each person.
Atherosclerosis is a slow, progressive
disease that may start in childhood. In some people this
disease progresses rapidly in their third decade. In others
it doesn't become threatening until they're in their 50s or
60s.
The vascular system is the body's
network of blood vessels. It includes the arteries, veins
and capillaries that carry blood to and from the heart.
Problems of the vascular system are common and can be
serious. Arteries can become thick and stiff, a problem
called arteriosclerosis. Blood clots can clog vessels and
block blood flow to the heart or brain. Weakened blood
vessels can burst, causing bleeding inside the body.
You are more likely to have vascular
disease as you get older. Other factors that make vascular
disease more likely include -
● Family history of vascular or heart diseases
● Pregnancy
● Illness or injury
● Long periods of sitting or standing still
● Any condition that affects the heart and blood vessels,
such as diabetes or high cholesterol
● Smoking
● Obesity
Losing weight, eating healthy foods,
being active and not smoking can help vascular disease.
Other treatments include medicines and surgery.
Coronary artery disease (CAD) is the
most common type of heart disease. It is the leading cause
of death in the United States in both men and women.
CAD happens when the arteries that
supply blood to heart muscle become hardened and narrowed.
This is due to the buildup of
cholesterol and other material, called plaque, on their
inner walls. As the buildup grows, less blood can flow
through the arteries. As a result, the heart muscle can't
get the blood or oxygen it needs. This can lead to chest
pain (angina)
or a
heart attack. Most heart attacks happen when a blood
clot suddenly cuts off the hearts' blood supply, causing
permanent heart damage.
Over time, CAD can also weaken the
heart muscle and contribute to
heart failure and
arrhythmias. Heart failure means the heart can't pump
blood well to the rest of the body. Arrhythmias are changes
in the normal beating rhythm of the heart.
According to the U.S. Centers for
Disease Control and Prevention, heart disease is the number
one killer of Americans and a major cause of disability.
About 29 percent of all U.S. deaths are from heart disease
(approximately 700,000 a year). Stroke is the leading cause
of disability in the United States and the third leading
cause of death. By reducing the incidence of
atherosclerosis, the risk of fatal heart attacks or strokes
would decrease significantly.
Coronary Artery
Bypass
According to the National Institutes of
Health, coronary artery bypass grafting is the most common
open heart surgery in the United States, with 500,000
procedures performed each year. It is one of only a few
surgical options to treat coronary artery disease, which is
the leading cause of death in the United States. During this
surgery, a healthy vein or artery from another part of the
body is connected to the blocked coronary artery to route
blood flow around a blocked passage. Current procedures are
limited, however, by the availability of healthy veins or
arteries as well as the patient’s ability to survive both
aspects of the procedure. Furthermore, many patients
experience significant pain in the area where the vein or
artery was removed. Using artificial veins or arteries
instead would reduce recovery time, reduce pain, and save
lives by making this type of surgery more available to
people who need it.
Editor’s Notes:
The FASEB Journal (http://www.fasebj.org)
is published by the Federation of American Societies for Experimental
Biology (FASEB) and is consistently ranked among the top three biology
journals worldwide by the Institute for Scientific Information. FASEB
comprises 21 nonprofit societies with more than 80,000 members, making
it the largest coalition of biomedical research associations in the
United States. FASEB advances biological science through collaborative
advocacy for research policies that promote scientific progress and
education and lead to improvements in human health.
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Atherosclerosis
is a type of arteriosclerosis. The name comes from the Greek
words athero (meaning gruel or paste) and sclerosis
(hardness). It's the term for the process of fatty
substances, cholesterol, cellular waste products, calcium
and fibrin (a clotting material in the blood) building up in
the inner lining of an artery. The buildup that results is
called plaque.