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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

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 M...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555548/
https://www.ncbi.nlm.nih.gov/pubmed/32957660
http://dx.doi.org/10.3390/ijms21186832
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author 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
author_facet 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
author_sort Azimzadeh, Omid
collection PubMed
description 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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spelling pubmed-75555482020-10-19 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 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 Int J Mol Sci Article 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. MDPI 2020-09-17 /pmc/articles/PMC7555548/ /pubmed/32957660 http://dx.doi.org/10.3390/ijms21186832 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555548/
https://www.ncbi.nlm.nih.gov/pubmed/32957660
http://dx.doi.org/10.3390/ijms21186832
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