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Chronic occupational exposure to ionizing radiation induces alterations in the structure and metabolism of the heart: A proteomic analysis of human formalin-fixed paraffin-embedded (FFPE) cardiac tissue.
Int. J. Mol. Sci. 21:6832 (2020)
Epidemiological studies on workers employed at the Mayak plutonium enrichment plant have demonstrated an association between external gamma ray exposure and an elevated risk of ischemic heart disease (IHD). In a previous study using fresh-frozen post mortem samples of the cardiac left ventricle of Mayak workers and non-irradiated controls, we observed radiation-induced alterations in the heart proteome, mainly downregulation of mitochondrial and structural proteins. As the control group available at that time was younger than the irradiated group, we could not exclude age as a confounding factor. To address this issue, we have now expanded our study to investigate additional samples using archival formalin-fixed paraffin-embedded (FFPE) tissue. Importantly, the control group studied here is older than the occupationally exposed (>500 mGy) group. Label-free quantitative proteomics analysis showed that proteins involved in the lipid metabolism, sirtuin signaling, mitochondrial function, cytoskeletal organization, and antioxidant defense were the most affected. A histopathological analysis elucidated large foci of fibrotic tissue, myocardial lipomatosis and lymphocytic infiltrations in the irradiated samples. These data highlight the suitability of FFPE material for proteomics analysis. The study confirms the previous results emphasizing the role of adverse metabolic changes in the radiation-associated IHD. Most importantly, it excludes age at the time of death as a confounding factor.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Ffpe ; Ionizing Radiation ; Occupational Exposure ; Proteomics ; Label-free ; Ppar Alpha ; Heart ; Ischemia ; Cardiovascular Disease; Sample Preparation; Mass-spectrometry; Mayak Pa; Disease; Expression; Proteins; Frozen; Cohort; Model
ISSN (print) / ISBN
1422-0067
e-ISSN
1661-6596
Quellenangaben
Volume: 21,
Issue: 18,
Article Number: 6832
Publisher
MDPI
Publishing Place
Basel
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Radiation Biology (ISB)
CF Metabolomics & Proteomics (CF-MPC)
Research Unit Analytical Pathology (AAP)
CF Metabolomics & Proteomics (CF-MPC)
Research Unit Analytical Pathology (AAP)
Grants
European Community's Seventh Framework Program (EURATOM)
Federal Medical Biological Agency (FMBA Russia)
Federal Office for Radiation Protection (BfS)
Federal Medical Biological Agency (FMBA Russia)
Federal Office for Radiation Protection (BfS)