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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
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
Zeitschrift
International Journal of Radiation Biology
Quellenangaben
Band: 90,
Heft: 7,
Seiten: 560-574
Verlag
Informa Healthcare
Verlagsort
London
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Radiation Biology (ISB)