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HDL cholesterol can reduce the inflammation that
leads to arterial plaque build-up. Atherosclerosis,
or hardening of the arteries, develops when plaque —
particularly cholesterol, fatty substances, cellular
debris and calcium deposits — accumulates on artery
walls.
Nathalie Niyonzima is a researcher at CEMIR, the
Centre of Molecular Inflammation Research at the
Norwegian University of Science and Technology NTNU.
“We’ve shown that “good cholesterol,” which consists
of high-density lipoproteins, dampens the chronic
inflammatory reaction that leads to atherosclerosis.
HDL cholesterol also has several other positive
characteristics,” says Nathalie Niyonzima.
“We’ve been looking for mechanisms that trigger and
influence an inflammatory response. The hope is to
move from lab studies to clinical trials,” says her
colleague Eivind Samstad. Their findings were
published in The Journal of Immunology this summer.
Cholesterol that accumulates in the blood vessel
walls results in the precipitation of cholesterol
crystals, previously thought to be inert.
However, a few years ago researchers at CEMIR
discovered that these cholesterol crystals actually
play an essential role in triggering the immune
response that leads to the development of
atherosclerosis.
As Niyonzima explains, the immune system identifies
the cholesterol crystals as harmful substances in
the body that need to be removed. But the antibodies
that come to the body’s defence are unable to break
down the crystals. The immune system calls out for
reinforcements, and more antibodies arrive, to no
avail. The immune reaction runs wild, and the
inflammation process escalates.
To test the effect of cholesterol crystals,
researchers used blood samples from healthy
volunteer donors – many of whom were colleagues in
the same department.
“In healthy blood samples all the natural components
are present, allowing us to study all the
mechanisms. When we added cholesterol crystals, we
saw that the complement system — an important part
of the innate immune system — was activated,” she
said.
Adding the cholesterol crystals triggered an immune
reaction that eventually got out of control,
resulting in inflammation.
“Researchers at CEMIR were the first to show that
cholesterol crystals can trigger inflammation by
activating the complement system. Now other studies
have confirmed this result,” says Niyonzima.
Now the researchers have gone further and looked at
the effect of HDL, also called “good cholesterol.”
It counteracts the effects of “bad cholesterol,” or
low-density lipoproteins (LDL).
Traditionally, HDL has been perceived as beneficial
because it carries away cholesterol from the artery
walls. It also has several other good qualities:
among other things, it is an antioxidant, and it
protects blood vessels’ surface cells. So it turns
out that the good cholesterol, or at least an
artificial variant of it, helps to slow the
inflammatory process caused by cholesterol crystals.
CEMIR researchers used reconstituted HDL, developed
by the Australian pharmaceutical company CSL Behring,
where one protein fraction is cultivated.
She adds that these findings suggest that it may be
necessary to supplement existing treatment regimens
for atherosclerosis.
Samstad took his doctorate at CEMIR and is now a
doctor at the hospital in Ålesund.
“Over the last decade, scientists have been
concentrating more on the inflammation associated
with atherosclerosis. But there’s still a lot of
debate about what triggers this inflammatory
response,” says Samstad.
Drugs that reduce LDL cholesterol levels in the
blood have been the main treatment for
atherosclerosis. Samstad believes that we’re now
seeing a shift toward a greater interest in
anti-inflammatory medications.
“When we go in and influence an important mechanism
like the immune system, it’s critical that we know
what we’re doing. We need to know what mechanisms
we’re affecting, and how,” he says.
So far, researchers have used blood from healthy
donors. Samstad hopes they have the opportunity to
follow up their study with an actual patient group,
such as people who have had heart attacks.
CEMIR has been designated a Centre of Excellence (SFF)
for research. A key question for the centre is how
inflammation may be so closely associated with many
seemingly different chronic diseases.
“We have a number of different projects that focus
on studying the inflammatory mechanisms and trying
to find ways to inhibit inflammation,” says the
centre’s director, Professor Terje Espevik.
The many exciting discoveries point towards larger
clinical trials. But studies such as these are too
expensive for a research centre like CEMIR.
“Our role is rather to conduct what is called
translational research, providing basic discoveries
that serve as the basis for clinical trials. The
pharmaceutical industry can take the ball from
here,” Espevik says.
In the wake of their rHDL project work, CEMIR
scientists are also working with another substance, Cyclodextrin,
which appears to have at least three important
characteristics: it dissolves cholesterol crystals,
it is powerfully anti-inflammatory, and it
transports cholesterol back to the liver (Link...).
For more information
The Journal of Immunology
“Reconstituted High-Density Lipoprotein Cholesterol
Attenuates Cholesterol Crystal-Induced Inflammatory
Responses by Reducing Complement Activation.”
Link...
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