title: The effect of oxidized low-density lipoprotein (ox-LDL) on radiation-induced endothelial-to-mesenchymal transition.
abstract: OBJECTIVE
  Radiation-induced cardiovascular disease is a potentially severe side-effect of thoracic radiotherapy treatment. Clinically, this delayed side-effect presents as a form of accelerated atherosclerosis several years after irradiation. As general endothelial dysfunction is known to be an initiating event in radiation-induced vascular damage, we examined the effects of radiation on endothelial cells in radiation-induced atherosclerosis.
  
  
  METHODS
  The effects of radiation on human aortic endothelial cells (HAoEC) were assessed by immunoblotting and immunofluorescence assays. Radiation-induced phenotypic changes of endothelial cells (ECs) were examined using atherosclerotic tissues of irradiated apoprotein E null (ApoE(-/-)) mice.
  
  
  RESULTS
  Radiation induced the HAoEC to undergo phenotypic conversion to form fibroblast-like cells, called the endothelial-to-mesenchymal transition (EndMT), which leads to the upregulation of mesenchymal cell markers such as alpha-smooth muscle actin (α-SMA), fibroblast specific protein-1 (FSP-1), and vimentin, and downregulation of endothelial cell-specific markers such as CD31 and vascular endothelial (VE)-cadherin. Furthermore, compared with low-density lipoprotein (LDL), oxidized low-density lipoprotein (ox-LDL) significantly augmented radiation-induced EndMT in HAoEC. These fibrotic phenotypes of ECs were found in atherosclerotic tissues of irradiated ApoE(-/-) mice with increased levels of ox-LDL.
  
  
  CONCLUSIONS
  Taken together, these observations suggest that ox-LDL accelerates radiation-induced EndMT and subsequently contributes to radiation-induced atherosclerosis, providing a novel target for the prevention of radiation-induced atherosclerosis.
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological & Medical Sciences, Seoul, Korea.
authors.forename: Miseon
authors.initials: M
authors.lastname: Kim
authors.forename: Seo-Hyun
authors.initials: SH
authors.lastname: Choi
authors.forename: Yeung Bae
authors.initials: YB
authors.lastname: Jin
authors.forename: Hae-June
authors.initials: HJ
authors.lastname: Lee
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Ji
authors.forename: Joon
authors.initials: J
authors.lastname: Kim
authors.forename: Yun-Sil
authors.initials: YS
authors.lastname: Lee
authors.forename: Yoon-Jin
authors.initials: YJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D050197:Atherosclerosis / Q000473:pathology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008297:Male; D008648:Mesoderm / Q000166:cytology* / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011833:Radiation Injuries, Experimental / Q000473:pathology
chemical_list: D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein