New insights into the development of vulnerable atherosclerotic plaques could lead to better treatment or prevention of heart attacks and strokes. In a report being published online in Nature Medicine, researchers at the Massachusetts General Hospital (MGH) Center for Systems Biology re-evaluated previous assumptions regarding the role of inflammatory cells in atherosclerosis and found that the process relies on proliferation of certain immune cells within plaques and not exclusively on the uptake of cells from the blood.
The prevailing theory of atherosclerosis has been that plaques grow by drawing white blood cells called monocytes in from the circulation. These monocytes then mature into macrophages, cells that ingest lipid and cholesterol molecules but remain within the plaques, leading to the buildup of a fatty core that contributes to the risk of plaque rupture. While it had been believed that each macrophage descended from a single monocyte that had entered a plaque, the MGH team found that proliferation of new macrophages within plaques is a major driver of their growth.
"Currently, there is quite a bit of interest in targeting inflammation as a way to treat vascular disease, and one of the ways to do so is by targeting the cells responsible, says Filip Swirski, PhD, of the MGH Center for Systems Biology, senior author of the Nature Medicine report. "We discovered that the atherosclerotic lesion is a very dynamic environment, and even though the macrophages within a lesion are fundamentally derived from monocytes, they do not require constant monocyte input to sustain their numbers."
In a series of experiments in mice, the MGH-CSB team first found that existing plaques within the aortas of animals fed a high-cholesterol diet showed evidence of a rapid and constant proliferation of macrophages that did not require the presence of monocytes in the blood. Although monocytes were needed for the initiation of atherosclerosis, once plaques had formed, macrophage proliferation became the primary mechanism for the further growth of plaques. The investigators also identified a receptor protein on macrophages that appears to contribute to their proliferation within plaques without the involvement of monocytes. While further study is required to determine whether the same processes occur in humans, the MGH team did find evidence of macrophage proliferation in plaques from human carotid arteries.
"I think this work will force some major re-evaluations," says Swirski, an assistant professor of Radiology 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 might actually be better than targeting circulating monocytes, since interrupting pathological processes within the plaques themselves could spare the beneficial immune responses mediated by monocytes."
Co-lead authors of the Nature Medicine article are Clinton Robbins, PhD, now at the University of Toronto, and Ingo Helgendorf, MD, MGH Center for Systems Biology. Additional co-authors are Georg Weber, MD, PhD, Igor Theurl, MD, Yoshiko Iwamoto, Jose-Luiz Figueiredo, MD, Rostic Gorbatov, Louisa Gerhardt, Herbert Lin, MD, PhD, Matthias Nahrendorf, MD, PhD, and Ralph Weissleder, MD, PhD, MGH-CSB; David Smyth, Caleb Zavitz, MD, PhD, Eric Shikatani and Mansoor Husain, MD, University of Toronto; Galina Sukhova, PhD, and Peter Libby, MD, Brigham and Women's Hospital; Michael Parsons, Mount Sinai Hospital, Toronto; and Nico van Rooijen, Free University Medical Center, Amsterdam. Support for the study includes National Institutes of Health grants 1R01HL095612, HHSN 268201000044C, P01-A154904, U24-CA092782, P50-CA086355.
Massachusetts General Hospital (http://www.massgeneral.org), founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $775 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.
Sue McGreevey | EurekAlert!
Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University
Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
24.02.2017 | Life Sciences
24.02.2017 | Life Sciences
24.02.2017 | Trade Fair News