Journal
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
Volume 90, Issue 7, Pages 560-574Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/09553002.2014.905724
Keywords
Gene expression; endothelial cells; chronic low dose rate ionizing radiation; senescence
Funding
- EU FP7 DoReMi [249689]
- EU FP7 Procardio project [295823]
- Federal Agency of Nuclear Control (FANC-AFCN, Belgium) [CO-90-13-3289-00]
- Swedish Radiation Safety Authority
- doctoral SCK.CEN/Ghent University grant
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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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