@article{8600339,
  abstract     = {{Background and Purpose : Epidemiological data suggests an excess risk of cardiovascular disease (CVD) at low doses (0.05 and 0.1 Gy) of ionizing radiation (IR). Furthermore, the underlying biological and molecular mechanisms of radiation-induced CVD are still unclear. Because damage to the endothelium could be critical in IR-related CVD, this study aimed to identify the effects of radiation on immortalized endothelial cells in the context of atherosclerosis. Material and 
Methods : Microarrays and RT-qPCR were used to compare the response of endothelial cells irradiated with a single X-ray dose (0.05, 0.1, 0.5, 2 Gy) measured after various post-irradiation (repair) times (1 day, 7 days, 14 days). To consolidate and mechanistically support the endothelial cell response to X-ray exposure identified via microarray analysis, DNA repair signaling (gamma H2AX/TP53BP1-foci quantification), cell cycle progression (BrdU/7AAD flow cytometric analysis), cellular senescence (beta-galactosidase assay with CPRG and IGFBP7 quantification) and pro-inflammatory status (IL6 and CCL2) was assessed. 
Results : Microarray results indicated persistent changes in cell cycle progression and inflammation. Cells underwent G1 arrest in a dose-dependent manner after high doses (0.5 and 2 Gy), which was compensated by increased proliferation after 1 week and almost normalized after 2 weeks. However, at this point irradiated cells showed an increased beta-Gal activity and IGFBP7 secretion, indicative of premature senescence. The production of pro-inflammatory cytokines IL6 and CCL2 was increased at early time points. 
Conclusions : IR induces pro-atherosclerotic processes in endothelial cells in a dose-dependent manner. These findings give an incentive for further research on the shape of the dose-response curve, as we show that even low doses of IR can induce premature endothelial senescence at later time points. Furthermore, our findings on the time-and dose-dependent response regarding differentially expressed genes, cell cycle progression, inflammation and senescence bring novel insights into the underlying molecular mechanisms of the endothelial response to X-ray radiation. This may in turn lead to the development of risk-reducing strategies to prevent IR-induced CVD, such as the use of cell cycle modulators and anti-inflammatory drugs as radioprotectors and/or radiation mitigators.}},
  articleno    = {{213}},
  author       = {{Baselet, Bjorn and Belmans, Niels and Coninx, Emma and Lowe, Donna and Janssen, Ann and Michaux, Arlette and Tabury, Kevin and Raj, Kenneth and Quintens, Roel and Benotmane, Mohammed A and Baatout, Sarah and Sonveaux, Pierre and Aerts, An}},
  issn         = {{1663-9812}},
  journal      = {{FRONTIERS IN PHARMACOLOGY}},
  keywords     = {{X-ray,endothelium,atherosclerosis,cardiovascular disease,cell cycle,DNA-DAMAGE RESPONSE,IONIZING-RADIATION,PREMATURE SENESCENCE,CURRENT KNOWLEDGE,APOE(-/-) MICE,HEART-DISEASE,ATHEROSCLEROSIS,PATHWAYS,EXPOSURE,RADIOTHERAPY}},
  language     = {{eng}},
  pages        = {{13}},
  title        = {{Functional gene analysis reveals cell cycle changes and inflammation in endothelial cells irradiated with a single X-ray dose}},
  url          = {{http://doi.org/10.3389/fphar.2017.00213}},
  volume       = {{8}},
  year         = {{2017}},
}

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