Low dose radiation response in endothelial cells as biological model for radiation-related cardiovascular risks

Below 0.5 Gy there is no clear dose-risk relationship for cardiovascular disease (CVD) risk. Biological understanding of radiation-related CVD is required for defining accurately the dose-risk relationship. The endothelium forms the inner layer of the cardiovascular system and its physiological actions maintain normal cardiovascular functioning. Endothelial cells are thus considered a critical target in radiation-related CVD. Therefore, we evaluated the low (<0.5 Gy) and high (2; 5 Gy) dose radiation response, with respect to DNA damage and repair, cell cycle progression and apoptosis, in primary human umbilical vein endothelial cells (HUVEC) and its immortalized derivative, the EA.hy926 cell line. We demonstrated for the first time that acute low doses of X-rays induce DNA damage and apoptosis in endothelial cells. More radiation-induced apoptosis occurred in EA.hy926 cells implying a higher radiosensitivity of EA.hy926 compared to HUVEC for this endpoint, which should be taken into account when using these cells as models for studying the endothelium radiation response. Furthermore, our results point to a non-linear dose-response relationship for DNA damage in endothelial cells. Overall, our findings indicating cellular effects below 0.5 Gy, may influence on the long term the current radio protection system that assumes a threshold dose for non-cancer effects