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Rombouts, C.* ; Aerts, A.L.* ; Quintens, R.* ; Baselet, B.* ; El-Saghire, H.* ; Harms-Ringdahl, M.* ; Haghdoost, S.* ; Janssen, A.* ; Michaux, A.* ; Yentrapalli, R. ; Benotmane, M.A.* ; van Oostveldt, P.M.* ; Baatout, S.*

Transcriptomic profiling suggests a role for IGFBP5 in premature senescence of endothelial cells after chronic low dose rate irradiation.

Int. J. Radiat. Biol. 90, 560-574 (2014)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
Purpose: Ionizing radiation has been recognized to increase the risk of cardiovascular diseases (CVD). However, there is no consensus concerning the dose-risk relationship for low radiation doses and a mechanistic understanding of low dose effects is needed. Material and methods: Previously, human umbilical vein endothelial cells (HUVEC) were exposed to chronic low dose rate radiation (1.4 and 4.1 mGy/h) during one, three and six weeks which resulted in premature senescence in cells exposed to 4.1 mGy/h. To gain more insight into the underlying signaling pathways, we analyzed gene expression changes in these cells using microarray technology. The obtained data were analyzed in a dual approach, combining single gene expression analysis and Gene Set Enrichment Analysis. Results: An early stress response was observed after one week of exposure to 4.1 mGy/h which was replaced by a more inflammation-related expression profile after three weeks and onwards. This early stress response may trigger the radiation-induced premature senescence previously observed in HUVEC irradiated with 4.1 mGy/h. A dedicated analysis pointed to the involvement of insulin-like growth factor binding protein 5 (IGFBP5) signaling in radiation-induced premature senescence. Conclusion: Our findings motivate further research on the shape of the dose-response and the dose rate effect for radiation-induced vascular senescence.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Chronic Low Dose Rate Ionizing Radiation ; Endothelial Cells ; Gene Expression ; Senescence; Gene Set Enrichment; Wide Expression Profiles; Factor-binding Protein-5; Cellular Senescence; Ionizing-radiation; Plasminogen-activator; Dna-damage; Replicative Senescence; Circulatory Disease; Leukocyte Adhesion
ISSN (print) / ISBN 0955-3002
e-ISSN 1362-3095
Journal International Journal of Radiation Biology
Quellenangaben Volume: 90, Issue: 7, Pages: 560-574 Article Number: , Supplement: ,
Publisher Informa Healthcare
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Radiation Biology (ISB)