Radiation Response of Human Cardiac Endothelial Cells Reveals a Central Role of the cGAS-STING Pathway in the Development of Inflammation

Philipp, Jos; Le Gleut, Ronan; Toerne, Christine von; Subedi, Prabal; Azimzadeh, Omid; Atkinson, Michael J.; Tapio, Soile

doi:10.3390/proteomes8040030

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Radiation Response of Human Cardiac Endothelial Cells Reveals a Central Role of the cGAS-STING Pathway in the Development of Inflammation

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Institute of Radiation Biology, Helmholtz Center Munich, German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany

Institute of Computational Biology, Helmholtz Center Munich, German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany

Research Unit Protein Science, Helmholtz Center Munich, German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany

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Federal Office for Radiation Protection, BfS, 85764 Neuherberg, Germany

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Chair of Radiation Biology, Technical University of Munich, 80333 Munich, Germany

Author to whom correspondence should be addressed.

Proteomes 2020, 8(4), 30; https://doi.org/10.3390/proteomes8040030

Received: 2 September 2020 / Revised: 6 October 2020 / Accepted: 19 October 2020 / Published: 26 October 2020

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Abstract

Radiation-induced inflammation leading to the permeability of the endothelial barrier may increase the risk of cardiovascular disease. The aim of this study was to investigate potential mechanisms in vitro at the level of the proteome in human coronary artery endothelial cells (HCECest2) that were exposed to radiation doses of 0, 0.25, 0.5, 2.0 and 10 Gy (60Co-γ). Proteomics analysis was performed using mass spectrometry in a label-free data-independent acquisition mode. The data were validated using bioinformatics and immunoblotting. The low- and moderate-dose-irradiated samples (0.25 Gy, 0.5 Gy) showed only scarce proteome changes. In contrast, an activation of DNA-damage repair, inflammation, and oxidative stress pathways was seen after the high-dose treatments (2 and 10 Gy). The level of the DNA damage response protein DDB2 was enhanced early at the 10 Gy dose. The expression of proteins belonging to the inflammatory response or cGAS-STING pathway (STING, STAT1, ICAM1, ISG15) increased in a dose-dependent manner, showing the strongest effects at 10 Gy after one week. This study suggests a connection between the radiation-induced DNA damage and the induction of inflammation which supports the inhibition of the cGAS-STING pathway in the prevention of radiation-induced cardiovascular disease. View Full-Text

Keywords: ionizing radiation; proteomics; inflammation; cGAS-STING-pathway; DDB2; endothelial cells; STAT1; data-independent acquisition

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MDPI and ACS Style

Philipp, J.; Le Gleut, R.; Toerne, C.v.; Subedi, P.; Azimzadeh, O.; Atkinson, M.J.; Tapio, S. Radiation Response of Human Cardiac Endothelial Cells Reveals a Central Role of the cGAS-STING Pathway in the Development of Inflammation. Proteomes 2020, 8, 30. https://doi.org/10.3390/proteomes8040030

AMA Style

Philipp J, Le Gleut R, Toerne Cv, Subedi P, Azimzadeh O, Atkinson MJ, Tapio S. Radiation Response of Human Cardiac Endothelial Cells Reveals a Central Role of the cGAS-STING Pathway in the Development of Inflammation. Proteomes. 2020; 8(4):30. https://doi.org/10.3390/proteomes8040030

Chicago/Turabian Style

Philipp, Jos, Ronan Le Gleut, Christine von Toerne, Prabal Subedi, Omid Azimzadeh, Michael J. Atkinson, and Soile Tapio. 2020. "Radiation Response of Human Cardiac Endothelial Cells Reveals a Central Role of the cGAS-STING Pathway in the Development of Inflammation" Proteomes 8, no. 4: 30. https://doi.org/10.3390/proteomes8040030

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Radiation Response of Human Cardiac Endothelial Cells Reveals a Central Role of the cGAS-STING Pathway in the Development of Inflammation

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