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

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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
chronic low dose rate ionizing radiation, endothelial cells, 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, Gene expression

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Chicago
Rombouts, Charlotte, An Aerts, Roel Quintens, Bjorn Baselet, Hussein El-Sahire, Mats Harms-Ringdahl, Siamak Haghdoost, et al. 2014. “Transcriptomic Profiling Suggests a Role for IGFBP5 in Premature Senescence of Endothelial Cells After Chronic Low Dose Irradiation.” International Journal of Radiation Biology 90 (7): 560–574.
APA
Rombouts, Charlotte, Aerts, A., Quintens, R., Baselet, B., El-Sahire, H., Harms-Ringdahl, M., Haghdoost, S., et al. (2014). Transcriptomic profiling suggests a role for IGFBP5 in premature senescence of endothelial cells after chronic low dose irradiation. INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 90(7), 560–574.
Vancouver
1.
Rombouts C, Aerts A, Quintens R, Baselet B, El-Sahire H, Harms-Ringdahl M, et al. Transcriptomic profiling suggests a role for IGFBP5 in premature senescence of endothelial cells after chronic low dose irradiation. INTERNATIONAL JOURNAL OF RADIATION BIOLOGY. 2014;90(7):560–74.
MLA
Rombouts, Charlotte, An Aerts, Roel Quintens, et al. “Transcriptomic Profiling Suggests a Role for IGFBP5 in Premature Senescence of Endothelial Cells After Chronic Low Dose Irradiation.” INTERNATIONAL JOURNAL OF RADIATION BIOLOGY 90.7 (2014): 560–574. Print.
@article{5775791,
  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.},
  author       = {Rombouts, Charlotte and Aerts, An and Quintens, Roel and Baselet, Bjorn and El-Sahire, Hussein and Harms-Ringdahl, Mats and Haghdoost, Siamak and Janssen, Ann and Michaux, Arlette and Yentrapalli, Ramesh and Benotmane, Mohammed Abderrafi and Van Oostveldt, Patric and Baatout, Sarah},
  issn         = {0955-3002},
  journal      = {INTERNATIONAL JOURNAL OF RADIATION BIOLOGY},
  keyword      = {chronic low dose rate ionizing radiation,endothelial cells,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,Gene expression},
  language     = {eng},
  number       = {7},
  pages        = {560--574},
  title        = {Transcriptomic profiling suggests a role for IGFBP5 in premature senescence of endothelial cells after chronic low dose irradiation},
  url          = {http://dx.doi.org/10.3109/09553002.2014.905724},
  volume       = {90},
  year         = {2014},
}

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