Key result
Oxidized LDL augments radiation-induced endothelial-to-mesenchymal transition versus LDL in human aortic endothelial cells.
Why the study?
Radiation-induced cardiovascular disease manifests as accelerated atherosclerosis years after thoracic radiotherapy, with endothelial dysfunction as an initiating event.
Oxidized LDL accelerates radiation-induced endothelial-to-mesenchymal transition, suggesting a potential mechanism and therapeutic target for radiation-induced atherosclerosis.
Low-dose irradiation induces persistent endothelial proteome changes and senescence in vitro; hypothesis-generating for radiation-induced atherosclerosis mechanisms, needs in vivo confirmation.
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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Kim et al. (2013) studied Radiation-induced atherosclerosis. Oxidized low-density lipoprotein (ox-LDL) vs. Low-density lipoprotein (LDL) was evaluated on Endothelial-to-mesenchymal transition (EndMT). Oxidized low-density lipoprotein significantly augmented radiation-induced endothelial-to-mesenchymal transition compared with low-density lipoprotein in human aortic endothelial cells.
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