title: Transcriptomic profiling suggests a role for IGFBP5 in premature senescence of endothelial cells after chronic low dose rate irradiation.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Our findings motivate further research on the shape of the dose-response and the dose rate effect for radiation-induced vascular senescence.
authors.affiliation: Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN , Mol , Belgium.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Rombouts
authors.forename: An
authors.initials: A
authors.lastname: Aerts
authors.forename: Roel
authors.initials: R
authors.lastname: Quintens
authors.forename: Bjorn
authors.initials: B
authors.lastname: Baselet
authors.forename: Hussein
authors.initials: H
authors.lastname: El-Saghire
authors.forename: Mats
authors.initials: M
authors.lastname: Harms-Ringdahl
authors.forename: Siamak
authors.initials: S
authors.lastname: Haghdoost
authors.forename: Ann
authors.initials: A
authors.lastname: Janssen
authors.forename: Arlette
authors.initials: A
authors.lastname: Michaux
authors.forename: Ramesh
authors.initials: R
authors.lastname: Yentrapalli
authors.forename: Mohammed Abderrafi
authors.initials: MA
authors.lastname: Benotmane
authors.forename: Patrick
authors.initials: P
authors.lastname: Van Oostveldt
authors.forename: Sarah
authors.initials: S
authors.lastname: Baatout
mesh_terms: D016922:Cellular Senescence / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D020869:Gene Expression Profiling; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects*; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism*; D015398:Signal Transduction / Q000528:radiation effects; D013997:Time Factors; D059467:Transcriptome / Q000528:radiation effects
chemical_list: D018975:Insulin-Like Growth Factor Binding Protein 5
keywords: Gene expression; chronic low dose rate ionizing radiation; endothelial cells; senescence