The effect of oxidized low-density lipoprotein (ox-LDL) on radiation-induced endothelial-to-mesenchymal transition

Miseon Kim, Seo Hyun Choi, Yeung Bae Jin, Hae June Lee, Young Hoon Ji, Joon Kim, Yun Sil Lee, Yoon Jin Lee

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Purpose: 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. Materials and 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.

Original languageEnglish
Pages (from-to)356-363
Number of pages8
JournalInternational Journal of Radiation Biology
Volume89
Issue number5
DOIs
Publication statusPublished - 2013 May 1

Fingerprint

Radiation
Endothelial Cells
Atherosclerosis
Radiation Effects
Apolipoproteins E
oxidized low density lipoprotein
Vimentin
LDL Lipoproteins
Immunoblotting
Fluorescent Antibody Technique
Smooth Muscle
Blood Vessels
Actins
Cardiovascular Diseases
Up-Regulation
Radiotherapy
Thorax
Down-Regulation
Fibroblasts
Phenotype

Keywords

  • Atherosclerosis
  • Endothelial- to-mesenchymal transition (EndMT)
  • Oxidized low-density lipoprotein (ox-LDL)
  • Radiation

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

Cite this

The effect of oxidized low-density lipoprotein (ox-LDL) on radiation-induced endothelial-to-mesenchymal transition. / Kim, Miseon; Choi, Seo Hyun; Jin, Yeung Bae; Lee, Hae June; Ji, Young Hoon; Kim, Joon; Lee, Yun Sil; Lee, Yoon Jin.

In: International Journal of Radiation Biology, Vol. 89, No. 5, 01.05.2013, p. 356-363.

Research output: Contribution to journalArticle

Kim, Miseon ; Choi, Seo Hyun ; Jin, Yeung Bae ; Lee, Hae June ; Ji, Young Hoon ; Kim, Joon ; Lee, Yun Sil ; Lee, Yoon Jin. / The effect of oxidized low-density lipoprotein (ox-LDL) on radiation-induced endothelial-to-mesenchymal transition. In: International Journal of Radiation Biology. 2013 ; Vol. 89, No. 5. pp. 356-363.
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AB - Purpose: 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. Materials and 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.

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