The research also suggests a new potential target in the treatment of atherosclerosis, a leading cause of cardiovascular disease and death globally.
The research team found that macrophages, white blood cells that drive atherosclerosis, replicate inside plaques. Moreover, this growth is not reliant on cells outside the plaques called monocytes, as scientists had assumed.
"Until now, the thinking was that inflammatory macrophages arise mainly from the recruitment of their precursors — monocytes — from the bloodstream," said Clint Robbins, lead author on the study and an Assistant Professor in U of T's Departments of Laboratory Medicine and Pathobiology, and Immunology. "Our study shows that the accumulation of macrophages also depends on their proliferation locally within the developing plaque."
The journal Nature Medicine published the study results today.
The impact of the research on clinical treatments could be large. Many pharmaceutical companies are pouring resources into potential therapies that can block the recruitment of white blood cells into plaques. But if macrophages self-sustain through local cell division, blocking recruitment may not be the best strategy.
"I think this work will force some major re-evaluations," said Filip Swirski, the study's principal investigator who is a scientist in the Center for Systems Biology at Massachusetts General Hospital and an Assistant Professor at Harvard Medical School. "People have been thinking of targeting monocyte influx to treat atherosclerosis, but they need to consider macrophage proliferation as an additional or alternative approach, especially in established disease."
That approach might be better than targeting circulating monocytes, since interrupting disease-causing processes within plaques could spare other beneficial immune responses that monocytes control, said Swirski.
As well, it could help improve the current standard of care in treating atherosclerosis: statin therapy. Statins, in addition to lowering blood lipids that contribute to plaque, have anti-inflammatory properties. The researchers are now looking at whether statins might limit the spread of macrophages within plaques.
"Additional targeting of macrophage proliferation may further decrease inflammation in atherosclerosis and prove clinically advantageous," said Robbins, who is also a scientist in the Toronto General Research Institute at University Health Network.
The researchers conducted their study in mice, and they caution that much more research is needed to see how the work will translate to humans. But encouragingly, they found evidence of macrophage growth in plaques from human carotid arteries.
Next, the team will compare macrophage proliferation to monocyte recruitment during different stages of atherosclerosis, and look at whether all macrophages, or only subsets, replicate.
The study was funded by the U.S. National Institutes of Health, the Massachusetts General Hospital, the Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, and the Department of Laboratory Medicine and Pathobiology at the University of Toronto.
This news release was partly adapted from a Massachusetts General Hospital release by Sue McGreevey.
Jim Oldfield | EurekAlert!
23.03.2017 | Technische Universität München
How prenatal maternal infections may affect genetic factors in Autism spectrum disorder
22.03.2017 | 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
23.03.2017 | Life Sciences
23.03.2017 | Power and Electrical Engineering
23.03.2017 | Earth Sciences