Hardened and inflamed arteries, atherosclerosis, can be very dangerous. The consequences of atherosclerosis are among the most common causes of death in industrialized nations; in particular heart attacks and strokes. Crystalline cholesterol can contribute to this life-threatening inflammation in the arteries. An international research team of immunologists and cardiologists from the University of Bonn has now discovered that the ring-shaped sugar known as "cyclodextrin" can prevent and even reduce these dangerous cholesterol deposits. The results are now being published in the journal "Science Translational Medicine."
It is always a challenge for researchers to find the right approach for tackling a scientific issue. Yet sometimes people without any particular medical expertise also provide important clues which then lead to real breakthroughs. This was the case with Chris Hempel from the USA whose twin daughters suffer from the rare "Niemann-Pick type C" disease.
In this disease, gene mutations cause the dysfunction of cholesterol transport in the cells. Those affected initially develop normally, but then in childhood there is a rapid worsening of neurological function, with cognitive and motor impairment.
Until Chris Hempel became active, there was no treatment for Niemann-Pick C. With the aid of scientists, the mother developed a novel therapy with the ring-shaped sugar "cyclodextrin" which leads to better elimination of excess cholesterol from brain cells. Clinical studies on this are currently being conducted in the USA.
Prof. Dr. Eicke Latz from the Institute of Innate Immunity at the University of Bonn is studying how crystalline cholesterol causes massive immune responses and leads to life-threatening inflammation in arterial walls. In 2010, he published a study in the renowned journal "Nature" on the connection between atherosclerosis and the immune system.
In this study, the team of researchers working with Prof. Latz demonstrated that cholesterol crystals can activate an important receptor complex of the innate immune system and thus increase the inflammatory response in artherosclerosis. This caught Chris Hempel's attention and she reported her experiences with cyclodextrin to the immunologist.
High-cholesterol diet for mice
With an international team of researchers from Germany, the USA, Norway, Australia and Sweden, the scientists from a variety of fields from the University Hospital Bonn, under the direction of Prof. Latz, investigated whether cyclodextrin also has an effect on atherosclerosis.
The researchers fed a particularly cholesterol-rich diet to mice for eight weeks and subcutaneously injected the animals with cyclodextrin. "They were far less affected by plaques in their blood vessels than a control group who did not receive any cyclodextrin," says Dr. Sebastian Zimmer from the Department of Medicine II of the University Hospital Bonn. The ring-shaped sugars apparently program the cells in a way that leads to better elimination of excess crystalline cholesterol and also to a reduction in the inflammation in blood vessels at the same time.
Cyclodextrin increases the natural breakdown of cholesterol in the cells
The transcription factor "liver-X-receptor" (LXR) is a key regulator of cholesterol metabolism and thus plays an important role in connection atherosclerosis. "If too much cholesterol is present, LXR gives a signal. As a result, genes responsible for the efflux from the cell are activated," reports Alena Grebe, doctoral student in Prof. Latz's team.
"In addition, this factor downregulates inflammation." If the gene for LXR was muted absent in mice, this signal cascade did not function and cyclodextrin did not show any effect. The ring-shaped sugar evidently fulfills the function of an intermediary which increases the natural mechanisms of cholesterol breakdown in the cells and additionally reduces the inflammatory response.
Using human atherosclerotic vessels, the team also investigated whether cyclodextrin has the same effect in humans as in mice. The researchers cultivated plaques which had been surgically removed from the carotid arteries of atherosclerosis patients in order to improve their blood flow. If cyclodextrin was mixed into the nutrient solution, the cells showed the same reprogramming as those of the rodents: the mechanisms for plaque reduction started up and the inflammatory response subsided.
The active substance is already on the market
Prof. Latz hopes that cyclodextrin can be further developed as a drug for the treatment of atherosclerosis. "It is already on the market as a pharmaceutical solubilizing agent. However, costly clinical studies are needed for the new application," says the immunologist from the University of Bonn. Chris Hempel who pointed out the active substance cyclodextrin is incidentally listed as a co-author in the journal publication.
Publication: Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming, “Science Translational Medicine”, DOI: 10.1126/scitranslmed.aad6100
Media contact information:
Prof. Dr. Eicke Latz
Director of the Institute of Innate Immunity
University of Bonn
Johannes Seiler | idw - Informationsdienst Wissenschaft
Laser activated gold pyramids could deliver drugs, DNA into cells without harm
24.03.2017 | Harvard John A. Paulson School of Engineering and Applied Sciences
What does congenital Zika syndrome look like?
24.03.2017 | University of California - San Diego
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy