TY - JOUR
T1 - Chronic occupational exposure to ionizing radiation induces alterations in the structure and metabolism of the heart
T2 - A proteomic analysis of human formalin-fixed paraffin-embedded (FFPE) cardiac tissue
AU - Azimzadeh, Omid
AU - Azizova, Tamara
AU - Merl-Pham, Juliane
AU - Blutke, Andreas
AU - Moseeva, Maria
AU - Zubkova, Olga
AU - Anastasov, Natasa
AU - Feuchtinger, Annette
AU - Hauck, Stefanie M.
AU - Atkinson, Michael J.
AU - Tapio, Soile
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/9/2
Y1 - 2020/9/2
N2 - 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.
AB - 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.
KW - Cardiovascular disease
KW - FFPE
KW - Heart
KW - Ionizing radiation
KW - Ischemia
KW - Label-free
KW - Occupational exposure
KW - PPAR alpha
KW - Proteomics
UR - http://www.scopus.com/inward/record.url?scp=85091173647&partnerID=8YFLogxK
U2 - 10.3390/ijms21186832
DO - 10.3390/ijms21186832
M3 - Article
C2 - 32957660
AN - SCOPUS:85091173647
SN - 1661-6596
VL - 21
SP - 1
EP - 21
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 18
M1 - 6832
ER -