title: Effect of ionizing radiation induced damage of endothelial progenitor cells in vascular regeneration.
abstract: OBJECTIVE
  A number of studies have revealed that stress signaling and subsequent stress responses in stem/progenitor cells are responsible for attenuated regeneration or degenerative disease. Because ionizing radiation (IR), which sensitizes diverse types of stem cells, reportedly induces cardio-circulatory diseases, we hypothesized that IR-induced vascular abnormalities are associated with defects in endothelial progenitor cells (EPCs) that are responsible for vascular homeostasis.
  
  
  RESULTS
  We used an irradiated mouse model to mimic the IR effect on vasculogenesis. Mouse EPCs isolated from irradiated mice and human EPCs exposed to IR were used for functional analysis and gene expression study. Under IR exposure, EPCs were depleted, and their function for vasculogenesis in vitro and in vivo was significantly reduced. In such IR-mediated stress responses, upregulating p21Cip1 and downregulating vascular endothelial growth factor (VEGF) were mediated by p53 transcriptional activity.
  
  
  CONCLUSIONS
  The results of the present study suggest that suppression of p53 would be clinically applicable to (1) minimize the functional defects in EPCs in order to prevent the onset of vascular diseases caused by radiation therapy or radiation exposure and also to (2) provide novel insight into the mechanisms of IR-induced vascular damage and a possible strategy to minimize vascular damage by IR.
authors.affiliation: College of Natural Sciences, Department of Life Sciences, Sogang University, Seoul, Korea.
authors.forename: Mi-Ok
authors.initials: MO
authors.lastname: Lee
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Song
authors.forename: Seokyun
authors.initials: S
authors.lastname: Jung
authors.forename: Seulgi
authors.initials: S
authors.lastname: Hur
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asahara
authors.forename: Hyongbum
authors.initials: H
authors.lastname: Kim
authors.forename: Sang-Mo
authors.initials: SM
authors.lastname: Kwon
authors.forename: Hyuk-Jin
authors.initials: HJ
authors.lastname: Cha
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000502:physiology* / Q000528:radiation effects; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000528:radiation effects*; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000502:physiology / Q000528:radiation effects*; D011839:Radiation, Ionizing; D012038:Regeneration / Q000502:physiology* / Q000528:radiation effects; D012039:Regional Blood Flow / Q000502:physiology; D015427:Reperfusion Injury / Q000503:physiopathology; D013234:Stem Cells / Q000166:cytology / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A