Single Dose Fe Ion Irradiation Highlights the Radiation Quality Dependent Nature of the Endothelial Cell Response to Ionizing Radiation Exposure

Background and Purpose. Radiotherapy is an essential tool for cancer treatment. In order to spare normal tissue and to reduce the risk of normal tissue complications, particle therapy is a method of choice. Although a large part of the healthy tissue can be spared due to improved depth dose characteristics, little is known about the underlying biological and molecular mechanisms of particle irradiation in healthy tissues, such as the vasculature. Elucidation of these vascular effects is also required in the context of long term space flights, as particle radiation is the main contributor to the radiation effects observed in space. Endothelial cells, forming the inner monolayer of all vasculature are especially sensitive to irradiation and, if damaged, contribute to radiation-induced cardiovascular disease.
Materials and Methods. Transcriptomics, proteomics and cytokine analyses were used to compare the response of endothelial cells irradiated with a single dose of X-ray or Fe ions (0 and 2.00 Gy) measured one and seven days post-irradiation. To support the observed inflammatory effects, endothelial cell adhesiveness to monocytes was assessed.
Results. Our results indicate time- and radiation quality-dependent changes in the endothelial cell response upon irradiation. The irradiation impact was more pronounced and longer lasting for Fe ions than for X-rays. Both radiation qualities decreased the expression of genes involved in cell-cell adhesion and enhanced the expression of proteins involved in caveolar-mediated endocytosis signaling. Endothelial inflammation and adhesiveness was increased with X-rays, but decreased after Fe ion exposure.
Conclusions. Fe ions induce pro-atherosclerotic processes in endothelial cells that are different in nature and/or kinetics than those induced by X-rays, highlighting the radiation quality-dependent differences in the induction and progression of cardiovascular diseases. Our findings give a better understanding of the underlying processes in endothelial cells after particle irradiation, a crucial aspect for the development of protective measures for cancer patients undergoing particle therapy as well for astronauts in space.