Scripps scientists create cholesterol-like molecule that reduces atherosclerosis
15 October 2014
Scientists at The Scripps Research Institute (TSRI) in the US
have synthesised a molecule that mimics high-density cholesterol and
shown it can reduce plaque build-up in arteries even when taken
The molecule, taken orally, improved blood cholesterol
levels and reduced plaque in just two weeks in mice strains that
were prone to atherosclerosis.
This research, published in the October issue of Journal of
Lipid Research, could lead to a new method for treating
atherosclerosis, which can cause heart attacks and strokes.
Good & bad cholesterol
To 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.
“HDL 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 and first author of the new
study. From the liver, the LDL is packaged for elimination from the
Using 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 blood. Once the synthetic peptide wraps around LDL
cholesterol, it removes it by mimicking the behaviour of apoA-1, a
protein of HDL, and carrying it to the liver for elimination.
A surprising finding
The researchers tested this synthetic peptide in a mouse strain
bred to be prone to atherosclerosis. The team originally used the
synthetic peptide in an experiment they thought would be 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.
After 10 weeks of treatment, the mice had a 40% reduction in
LDL cholesterol in their blood and a 50% reduction
in the size of plaque lesions in their hearts. Similar results were
obtained using nanolipids of the corresponding monomeric peptide.
“We were definitely surprised at the results in the oral feeding
studies,” said Assistant Professor of Chemistry Luke Leman. “We’ve
repeated it many times.”
Many 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 for atherosclerosis.
The researchers also reported no signs of increased inflammation
in the blood or toxicity after 10 weeks of the peptide treatment.
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.
Yannan Zhao et al. Journal of Lipid Research, Published, JLR Papers in Press,
June 29, 2014, DOI 10.1194/jlr.M049262.
the Journal of Lipid
Research also published a commentary on the work, available at