Single exposure to radiation produces early anti-angiogenic effects in mouse aorta
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Radiation exposure can increase the risk for many non-malignant physiological complications, including cardiovascular disease. We have previously demonstrated that ionizing radiation can induce endothelial dysfunction, which contributes to increased vascular stiffness. In this study, we demonstrate that gamma radiation exposure reduced endothelial cell viability or proliferative capacity using an in vitro aortic angiogenesis assay. Segments of mouse aorta were embedded in a Matrigel-media matrix 1 day after mice received whole-body gamma irradiation between 0 and 20 Gy. Using three-dimensional phase contrast microscopy, we quantified cellular outgrowth from the aorta. Through fluorescent imaging of embedded aortas from Tie2GFP transgenic mice, we determined that the cellular outgrowth is primarily of endothelial cell origin. Significantly less endothelial cell outgrowth was observed in aortas of mice receiving radiation of 5, 10, and 20 Gy radiation, suggesting radiation-induced endothelial injury. Following 0.5 and 1 Gy doses of whole-body irradiation, reduced outgrowth was still detected. Furthermore, outgrowth was not affected by the location of the aortic segments excised along the descending aorta. In conclusion, a single exposure to gamma radiation significantly reduces endothelial cell outgrowth in a dose-dependent manner. Consequently, radiation exposure may inhibit re-endothelialization or angiogenesis after a vascular injury, which would impede vascular recovery.
KeywordsGamma Radiation Endothelial Progenitor Cell Endothelial Cell Outgrowth Angiogenic Potential Mouse Aorta
We would like to thank Dr. Aleksander S. Popel, Dr. Emmanouil D. Karagiannis, and Jacob Koskimaki of Johns Hopkins University for their assistance with the aortic angiogenesis assay. This research is supported largely in part by grants from the National Aeronautics and Space Administration (NNJ05HF03G) and National Space Biomedical Research Institute (NCC 9-58-CA01301).
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