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Azimzadeh, O. ; von Toerne, C. ; Subramanian, V. ; Sievert, W.* ; Multhoff, G.* ; Atkinson, M.J. ; Tapio, S.

Data-independent acquisition proteomics reveals long-term biomarkers in the serum of C57BL/6J mice following local high-dose heart irradiation.

Front. Publ. Health 9:678856 (2021)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Background and Purpose: Cardiotoxicity is a well-known adverse effect of radiation therapy. Measurable abnormalities in the heart function indicate advanced and often irreversible heart damage. Therefore, early detection of cardiac toxicity is necessary to delay and alleviate the development of the disease. The present study investigated long-term serum proteome alterations following local heart irradiation using a mouse model with the aim to detect biomarkers of radiation-induced cardiac toxicity. Materials and Methods: Serum samples from C57BL/6J mice were collected 20 weeks after local heart irradiation with 8 or 16 Gy X-ray; the controls were sham-irradiated. The samples were analyzed by quantitative proteomics based on data-independent acquisition mass spectrometry. The proteomics data were further investigated using bioinformatics and ELISA. Results: The analysis showed radiation-induced changes in the level of several serum proteins involved in the acute phase response, inflammation, and cholesterol metabolism. We found significantly enhanced expression of proinflammatory cytokines (TNF-α, TGF-β, IL-1, and IL-6) in the serum of the irradiated mice. The level of free fatty acids, total cholesterol, low-density lipoprotein (LDL), and oxidized LDL was increased, whereas that of high-density lipoprotein was decreased by irradiation. Conclusions: This study provides information on systemic effects of heart irradiation. It elucidates a radiation fingerprint in the serum that may be used to elucidate adverse cardiac effects after radiation therapy.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Biomarker ; Cardiac Lipid Metabolism ; Data-independent Acquisition ; Inflammation ; Ionizing Radiation ; Proteomics ; Radiation Therapy ; Radiation-induced Heart Disease; Low-density-lipoprotein; Cardiovascular-disease; Myocardial-infarction; Inflammatory Markers; Ionizing-radiation; Endothelial-cells; Immune-complexes; Gene-expression; Down-regulation; Ppar-alpha
ISSN (print) / ISBN 2296-2565
e-ISSN 2296-2565
Zeitschrift Frontiers in Public Health
Quellenangaben Band: 9, Heft: , Seiten: , Artikelnummer: 678856 Supplement: ,
Verlag Frontiers
Verlagsort Lausanne
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Radiation Medicine (IRM)
CF Metabolomics & Proteomics (CF-MPC)
Institute of Biological and Medical Imaging (IBMI)
Förderungen German Academic Exchange Service (DAAD)
Federal Ministry of Education and Research of Germany (BMBF)