You can manage bookmarks using lists, please log in to your user account for this.
Media type:
E-Article
Title:
Radiation Response of Human Cardiac Endothelial Cells Reveals a Central Role of the cGAS-STING Pathway in the Development of Inflammation
Contributor:
Philipp, Jos;
Le Gleut, Ronan;
Toerne, Christine von;
Subedi, Prabal;
Azimzadeh, Omid;
Atkinson, Michael J.;
Tapio, Soile
imprint:
MDPI AG, 2020
Published in:Proteomes
Language:
English
DOI:
10.3390/proteomes8040030
ISSN:
2227-7382
Origination:
Footnote:
Description:
<jats:p>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.</jats:p>