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Azimzadeh, O.* ; Merl-Pham, J. ; Subramanian, V.* ; Oleksenko, K. ; Krumm, F.* ; Mancuso, M.* ; Pasquali, E.* ; Tanaka, I.B.* ; Tanaka, S.* ; Atkinson, M.J. ; Tapio, S. ; Moertl, S.*

Late effects of chronic low dose rate total body irradiation on the heart proteome of ApoE-/- mice resemble premature cardiac ageing.

Cancers 15:21 (2023)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Recent epidemiologic studies support an association between chronic low-dose radiation exposure and the development of cardiovascular disease (CVD). The molecular mechanisms underlying the adverse effect of chronic low dose exposure are not fully understood. To address this issue, we have investigated changes in the heart proteome of ApoE deficient (ApoE-/-) C57Bl/6 female mice chronically irradiated for 300 days at a very low dose rate (1 mGy/day) or at a low dose rate (20 mGy/day), resulting in cumulative whole-body doses of 0.3 Gy or 6.0 Gy, respectively. The heart proteomes were compared to those of age-matched sham-irradiated ApoE-/- mice using label-free quantitative proteomics. Radiation-induced proteome changes were further validated using immunoblotting, enzyme activity assays, immunohistochemistry or targeted transcriptomics. The analyses showed persistent alterations in the cardiac proteome at both dose rates; however, the effect was more pronounced following higher dose rates. The altered proteins were involved in cardiac energy metabolism, ECM remodelling, oxidative stress, and ageing signalling pathways. The changes in PPARα, SIRT, AMPK, and mTOR signalling pathways were found at both dose rates and in a dose-dependent manner, whereas more changes in glycolysis and ECM remodelling were detected at the lower dose rate. These data provide strong evidence for the possible risk of cardiac injury following chronic low dose irradiation and show that several affected pathways following chronic irradiation overlap with those of ageing-associated heart pathology.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Ampk ; Pparα ; Sirt ; Tbi ; Tgfβ ; Ageing ; Cardiovascular Disease ; Chronic Exposure ; Heart ; Ionising Radiation ; Oxidative Stress ; Proteomics; Ionizing-radiation; Endothelial-cells; Longevity Genes; Ppar-alpha; Label-free; Hypertrophy; Activation; Exposure; Disease; Akt
ISSN (print) / ISBN 2072-6694
Journal Cancers
Quellenangaben Volume: 15, Issue: 13, Pages: , Article Number: 21 Supplement: ,
Publisher MDPI
Publishing Place St Alban-anlage 66, Ch-4052 Basel, Switzerland
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Radiation Biology (ISB)
CF Metabolomics & Proteomics (CF-MPC)