and Medicine for Seniors
‘Good’ Cholesterol Wins Fight to Reduce Plaque Buildup
toward new method for preventing plaque buildup in the arteries that can
cause heart attacks and strokes
10, 2014 - Scientists at The Scripps Research Institute (TSRI) have
created a synthetic molecule that mimics “good” cholesterol and have
shown it can reduce plaque buildup in the arteries of animal models. The
molecule, taken orally, improved cholesterol in just two weeks.
research, published in the October issue of Journal of Lipid Research,
points scientists toward a new method for treating atherosclerosis, a
condition where plaque buildup in the arteries can cause heart attacks
“Atherosclerosis is the number one killer in the developed world,” said
TSRI Professor M. Reza Ghadiri, senior author of the new study with TSRI
Assistant Professor of Chemistry Luke Leman. “This research clears a big
step toward clinical implementation of new therapies.”
combat atherosclerosis, researchers are looking for new ways to target
and remove low-density lipoprotein (LDL) cholesterol (commonly known as
“bad” cholesterol) from the body. Though the body needs some LDL to stay
healthy, high levels lead to dangerous plaque buildups. In contrast,
high-density lipoprotein (HDL) cholesterol (“good” cholesterol) is known
for its protective effects.
is like a taxi in the bloodstream; it takes the LDL cholesterol out of
the blood and delivers it to the liver,” said Yannan Zhao, a
postdoctoral researcher in Ghadiri’s lab and first author of the new
study. From the liver, the LDL is packaged for elimination from the
a method reported by the researchers last year in the Journal of the
American Chemical Society, the team created a “nanopeptide” to have
three arm-like structures that can wrap around cholesterol and fats in
the synthetic peptide wraps around LDL cholesterol, it removes it by
mimicking the behavior of apoA-1, a protein of HDL, and carrying it to
the liver for elimination.
collaboration with Linda Curtiss, formerly a faculty member at TSRI, and
Bruce Maryanoff, formerly at Johnson & Johnson and currently a visiting
scholar at TSRI, the researchers tested this synthetic peptide in a
mouse model prone to atherosclerosis.
team originally used the synthetic peptide in an experiment the
researchers thought was a gamble. They gave it to mice in their drinking
water, but assumed their digestive acids might break down the peptide
before it got a chance to interact with its target and modify LDL
cholesterol. To their surprise, it worked.
10 weeks of treatment, the mice had a 40 percent reduction in
potentially harmful cholesterol in their blood and a 50 percent
reduction in the size of plaque lesions in their hearts.
were definitely surprised at the results in the oral feeding studies,”
said Leman. “We’ve repeated it many times.”
cholesterol treatments currently in development rely on an injection,
not a pill. With the option of an orally effective peptide, Ghadiri
believes researchers are closer to developing an accessible new therapy
researchers also reported no signs of increased inflammation in the
blood or toxicity after 10 weeks of the peptide treatment.
Studies Point to Gut
Ghadiri and his team are now investigating exactly how the synthetic
peptide works in the intestines and the possibility that it interacts
with beneficial microbes. The researchers believe that finding new
targets in the gastrointestinal tract could lead to new therapies for
many more diseases.
“That’s one of the fun things in science—now we get to follow up on
these different avenues,” said Leman.
addition to Ghadiri, Leman, Zhao, Curtiss and Maryanoff, other
contributors to the study, “In vivo efficacy of HDL-like nanolipid
particles containing multivalent peptide mimetics of apolipoprotein
A-1,” are Audrey S. Black and David J. Bonnet of TSRI.
Support for this study came from the National Institutes of Health and
the American Heart Association Western States Affiliate.
About The Scripps Research Institute
Scripps Research Institute (TSRI) reports to be one of the world's
largest independent, not-for-profit organizations focusing on research
in the biomedical sciences. TSRI is internationally recognized for its
contributions to science and health, including its role in laying the
foundation for new treatments for cancer, rheumatoid arthritis,
hemophilia, and other diseases. An institution that evolved from the
Scripps Metabolic Clinic founded by philanthropist Ellen Browning
Scripps in 1924, the institute now employs about 3,000 people on its
campuses in La Jolla, CA, and Jupiter, FL, where its renowned
scientists—including TWO Nobel laureates—work toward their next
discoveries. The institute's graduate program, which awards PhD degrees
in biology and chemistry, ranks among the top ten of its kind in the
nation. For more information, see