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Prevention of radiotherapy-induced arterial inflammation by interleukin-1 blockade

AIMS: Radiotherapy-induced cardiovascular disease is an emerging problem in a growing population of cancer survivors where traditional treatments, such as anti-platelet and lipid-lowering drugs, have limited benefits. The aim of the study was to investigate vascular inflammatory patterns in human ca...

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Autores principales: Christersdottir, Tinna, Pirault, John, Gisterå, Anton, Bergman, Otto, Gallina, Alessandro L, Baumgartner, Roland, Lundberg, Anna M, Eriksson, Per, Yan, Zhong-Qun, Paulsson-Berne, Gabrielle, Hansson, Göran K, Olofsson, Peder S, Halle, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685328/
https://www.ncbi.nlm.nih.gov/pubmed/31081038
http://dx.doi.org/10.1093/eurheartj/ehz206
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author Christersdottir, Tinna
Pirault, John
Gisterå, Anton
Bergman, Otto
Gallina, Alessandro L
Baumgartner, Roland
Lundberg, Anna M
Eriksson, Per
Yan, Zhong-Qun
Paulsson-Berne, Gabrielle
Hansson, Göran K
Olofsson, Peder S
Halle, Martin
author_facet Christersdottir, Tinna
Pirault, John
Gisterå, Anton
Bergman, Otto
Gallina, Alessandro L
Baumgartner, Roland
Lundberg, Anna M
Eriksson, Per
Yan, Zhong-Qun
Paulsson-Berne, Gabrielle
Hansson, Göran K
Olofsson, Peder S
Halle, Martin
author_sort Christersdottir, Tinna
collection PubMed
description AIMS: Radiotherapy-induced cardiovascular disease is an emerging problem in a growing population of cancer survivors where traditional treatments, such as anti-platelet and lipid-lowering drugs, have limited benefits. The aim of the study was to investigate vascular inflammatory patterns in human cancer survivors, replicate the findings in an animal model, and evaluate whether interleukin-1 (IL-1) inhibition could be a potential treatment. METHODS AND RESULTS: Irradiated human arterial biopsies were collected during microvascular autologous free tissue transfer for cancer reconstruction and compared with non-irradiated arteries from the same patient. A mouse model was used to study the effects of the IL-1 receptor antagonist, anakinra, on localized radiation-induced vascular inflammation. We observed significant induction of genes associated with inflammasome biology in whole transcriptome analysis of irradiated arteries, a finding supported by elevated protein levels in irradiated arteries of both, pro-caspase and caspase-1. mRNA levels of inflammasome associated chemokines CCL2, CCL5 together with the adhesion molecule VCAM1, were elevated in human irradiated arteries as was the number of infiltrating macrophages. A similar pattern was reproduced in Apoe−/− mouse 10 weeks after localized chest irradiation with 14 Gy. Treatment with anakinra in irradiated mice significantly reduced Ccl2 and Ccl5 mRNA levels and expression of I-A(b). CONCLUSION: Anakinra, administered directly after radiation exposure for 2 weeks, ameliorated radiation induced sustained expression of inflammatory mediators in mice. Further studies are needed to evaluate IL-1 blockade as a treatment of radiotherapy-induced vascular disease in a clinical setting.
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spelling pubmed-66853282019-08-12 Prevention of radiotherapy-induced arterial inflammation by interleukin-1 blockade Christersdottir, Tinna Pirault, John Gisterå, Anton Bergman, Otto Gallina, Alessandro L Baumgartner, Roland Lundberg, Anna M Eriksson, Per Yan, Zhong-Qun Paulsson-Berne, Gabrielle Hansson, Göran K Olofsson, Peder S Halle, Martin Eur Heart J Basic Science AIMS: Radiotherapy-induced cardiovascular disease is an emerging problem in a growing population of cancer survivors where traditional treatments, such as anti-platelet and lipid-lowering drugs, have limited benefits. The aim of the study was to investigate vascular inflammatory patterns in human cancer survivors, replicate the findings in an animal model, and evaluate whether interleukin-1 (IL-1) inhibition could be a potential treatment. METHODS AND RESULTS: Irradiated human arterial biopsies were collected during microvascular autologous free tissue transfer for cancer reconstruction and compared with non-irradiated arteries from the same patient. A mouse model was used to study the effects of the IL-1 receptor antagonist, anakinra, on localized radiation-induced vascular inflammation. We observed significant induction of genes associated with inflammasome biology in whole transcriptome analysis of irradiated arteries, a finding supported by elevated protein levels in irradiated arteries of both, pro-caspase and caspase-1. mRNA levels of inflammasome associated chemokines CCL2, CCL5 together with the adhesion molecule VCAM1, were elevated in human irradiated arteries as was the number of infiltrating macrophages. A similar pattern was reproduced in Apoe−/− mouse 10 weeks after localized chest irradiation with 14 Gy. Treatment with anakinra in irradiated mice significantly reduced Ccl2 and Ccl5 mRNA levels and expression of I-A(b). CONCLUSION: Anakinra, administered directly after radiation exposure for 2 weeks, ameliorated radiation induced sustained expression of inflammatory mediators in mice. Further studies are needed to evaluate IL-1 blockade as a treatment of radiotherapy-induced vascular disease in a clinical setting. Oxford University Press 2019-08-07 2019-05-12 /pmc/articles/PMC6685328/ /pubmed/31081038 http://dx.doi.org/10.1093/eurheartj/ehz206 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Basic Science
Christersdottir, Tinna
Pirault, John
Gisterå, Anton
Bergman, Otto
Gallina, Alessandro L
Baumgartner, Roland
Lundberg, Anna M
Eriksson, Per
Yan, Zhong-Qun
Paulsson-Berne, Gabrielle
Hansson, Göran K
Olofsson, Peder S
Halle, Martin
Prevention of radiotherapy-induced arterial inflammation by interleukin-1 blockade
title Prevention of radiotherapy-induced arterial inflammation by interleukin-1 blockade
title_full Prevention of radiotherapy-induced arterial inflammation by interleukin-1 blockade
title_fullStr Prevention of radiotherapy-induced arterial inflammation by interleukin-1 blockade
title_full_unstemmed Prevention of radiotherapy-induced arterial inflammation by interleukin-1 blockade
title_short Prevention of radiotherapy-induced arterial inflammation by interleukin-1 blockade
title_sort prevention of radiotherapy-induced arterial inflammation by interleukin-1 blockade
topic Basic Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685328/
https://www.ncbi.nlm.nih.gov/pubmed/31081038
http://dx.doi.org/10.1093/eurheartj/ehz206
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