Reoxygenation of hypoxic coronary smooth muscle cells amplifies growth-retarding effects of ionizing irradiation
Hypoxic coronary smooth muscle cells (HCSMCs) are potential targets for brachytherapy to prevent restenosis after percutaneous transluminal angioplasty. It is unclear whether gene expression, apoptosis rate and production of reactive oxygen species of these cells undergoing alpha-irradiation are changed by reoxygenation. Hypoxic and reoxygenated HCSMCs were irradiated with alpha-radiation at single doses of 4, 8 and 16 Gy using a 60Co-source. Vascular endothelial growth factor (VEGF) gene expression was dramatically suppressed in reoxygenated versus hypoxic HCSMCs independent of the radiation dose. Likewise, hypoxia induced factor 1alpha (HIF-1alpha)expression was suppressed in reoxygenated versus hypoxic HCSMCs. Production of reactive oxygen species and apoptosis rate after irradiation were increased significantly in reoxygenated versus hypoxic HCSMCs. Reoxygenation of hypoxic HCSMCs markedly amplifies growth-retarding effects of ionizing irradiation via induction of HIF-1-alpha. On the basis of these findings, oxygenating radiosensitizers should be analysed with regard to suitablility for coronary brachytherapy to prevent restenosis.
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