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

Division of Radiation Effects, Korea Institute of Radiological & Medical Sciences, Seoul, Korea.

International journal of radiation biology 2013 May

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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. 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. 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. 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.

Citation

Miseon Kim, Seo-Hyun Choi, Yeung Bae Jin, Hae-June Lee, Young Hoon Ji, Joon Kim, Yun-Sil Lee, Yoon-Jin Lee. The effect of oxidized low-density lipoprotein (ox-LDL) on radiation-induced endothelial-to-mesenchymal transition. International journal of radiation biology. 2013 May;89(5):356-63