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

Abstract

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.

Keywords::

• Gene expression
• endothelial cells
• chronic low dose rate ionizing radiation
• senescence

Acknowledgements

This study was funded by the EU FP7 DoReMi (grant agreement 249689) on ‘low dose research towards multidisciplinary integration’, the EU FP7 Procardio project (grant agreement 295823) and by the Federal Agency of Nuclear Control (FANC-AFCN, Belgium), (grant agreement: CO-90-13-3289-00). Harms-Ringdahl M. has received support for these studies from the Swedish Radiation Safety Authority. Rombouts C. is supported by a doctoral SCK•CEN/Ghent University grant.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.