Findings Show The Force of Blood Flow Has Anti-Inflammatory
PA) - Scientists have found a new way in which exercise
may protect against heart disease. Increased blood flow
can mimic the powerful anti-inflammatory actions of
certain glucocorticoid steroid drugs, according to researchers
at the University of Pennsylvania's Institute
for Medicine and Engineering. The researchers discovered
that an increase in shear stress - the drag force exerted
by blood flowing over endothelial cells that line blood
vessels - results in the same sort of anti-inflammatory
events normally associated with high doses of steroids.
Their findings will be presented in the January 24th
online edition of Circulation Research: Journal of
the American Heart Association, followed by the
print edition of the journal on February 21st.
"Inflammation in blood vessels has been linked
to atherosclerosis, a hardening of the arteries, and
here we see how the physical force of blood flow can
cause cells to produce their own anti-inflammatory response,"
said Scott L. Diamond, PhD, director of the Penn's
Biotechnology Program and a professor of chemical and
biomolecular engineering at Penn's School of Engineering
and Applied Science. "Conceivably, exercise provides
the localized benefits of glucocorticoids - just as
potent as high doses of steroids, yet without all the
systemic side effects of taking the drugs themselves."
"Perhaps this is a natural way in which exercise
helps protect the vessels, by stimulating an anti-inflammatory
program when the vessels are exposed to elevated blood
flow. We're not talking about running a marathon here,
we're just talking about getting the blood moving at
high arterial levels," said Diamond.
It is the first direct evidence that the mechanical
effects of blood flow have anti-inflammatory properties.
According to their findings, shear stress can activate
glucocorticoid receptors (GR) to enter the nucleus of
the cells, an event normally triggered by glucocorticoid
steroids. Once inside the nucleus, the activated GR
binds to the DNA to turn genes on and off.
Diamond and his colleagues studied the effect of shear
stress on glucocorticoid receptors in endothelial cells
grown in culture by recreating in the laboratory the
flow environment of the large arteries. Sustained shear
stress - in the form of a steady stream of liquid flowing
across the cell culture - caused GRs to move into the
cell nuclei where they triggered the transcription of
a specially designed reporter gene. In fact, the effect
of shear stress alone had the same effect as dexamethasone,
a glucocorticoid steroid used to treat inflammation.
The researchers helped confirmed these findings in
vivo by examining a portion of the human mammary
artery and discovering that the blood flow had indeed
caused GR to be localized in the nucleus of the endothelial
cells. While the anti-inflammatory effects of exercise
training has yet to be documented in vivo, Diamond
believes the findings are applicable to living blood
"Think of blood flow as a stream: whenever a stream
branches off you get small areas of recirculation eddies
or pools of stagnant water. These same situations of
disturbed flow irritate the endothelium. When blood
vessels branch off, all the arterial flotsam - fats
and activated blood cells - can clump and stick at these
hot spots for atherosclerotic plaque formation,"
said Diamond. "Perhaps, elevated blood flow may
alter these disease prone regions to relieve some of
the localized inflammation."
The Institute for Medicine and Engineering was established
jointly by Penn's School of Medicine and Penn's School
of Engineering and Applied Science. Its focus is on
interdisciplinary research and education fundamental
to the application of advances in the treatment of disease.
Other Penn researchers involved in this study include
Julie Y. Ji and Huiyan Jing of the Institute for Medicine
and Engineering. Funding for this research comes from
the National Institutes of Health.
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