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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

1
Helmholtz Zentrum München—German Research Centre for Environmental Health GmbH, Institute of Radiation Biology, 85764 Neuherberg, Germany
2
Southern Urals Biophysics Institute (SUBI), Russian Federation, 456780 Ozyorsk, Russia
3
Helmholtz Zentrum München—German Research Centre for Environmental Health, Research Unit Protein Science, 80939 Munich, Germany
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Helmholtz Zentrum München—German Research Centre for Environmental Health GmbH, Research Unit Analytical Pathology, 85764 Neuherberg, Germany
5
Chair of Radiation Biology, Technical University of Munich, 81675 Munich, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(18), 6832; https://doi.org/10.3390/ijms21186832
Received: 19 June 2020 / Revised: 14 September 2020 / Accepted: 14 September 2020 / Published: 17 September 2020
(This article belongs to the Section Molecular Biology)
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. View Full-Text
Keywords: FFPE; ionizing radiation; occupational exposure; proteomics; label-free; PPAR alpha; heart; ischemia; cardiovascular disease FFPE; ionizing radiation; occupational exposure; proteomics; label-free; PPAR alpha; heart; ischemia; cardiovascular disease
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MDPI and ACS Style

Azimzadeh, O.; Azizova, T.; Merl-Pham, J.; Blutke, A.; Moseeva, M.; Zubkova, O.; Anastasov, N.; Feuchtinger, A.; Hauck, S.M.; Atkinson, M.J.; Tapio, S. 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. 2020, 21, 6832. https://doi.org/10.3390/ijms21186832

AMA Style

Azimzadeh O, Azizova T, Merl-Pham J, Blutke A, Moseeva M, Zubkova O, Anastasov N, Feuchtinger A, Hauck SM, Atkinson MJ, Tapio S. 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. International Journal of Molecular Sciences. 2020; 21(18):6832. https://doi.org/10.3390/ijms21186832

Chicago/Turabian Style

Azimzadeh, Omid; Azizova, Tamara; Merl-Pham, Juliane; Blutke, Andreas; Moseeva, Maria; Zubkova, Olga; Anastasov, Natasa; Feuchtinger, Annette; Hauck, Stefanie M.; Atkinson, Michael J.; Tapio, Soile. 2020. "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, no. 18: 6832. https://doi.org/10.3390/ijms21186832

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