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After radiotherapy treatment, there is an increased incidence of localized atherosclerosis in patients with Hodgkin's disease, breast cancer, and head and neck cancer. Here, we established a mouse model to study the development and progression of radiation-induced atherosclerosis and to compare the phenotype of these lesions with age-related atherosclerosis. Atherosclerosis-prone ApoE^−/− mice fed a regular chow diet received single radiation doses of 14 Gy or sham treatments (0 Gy) to the neck, including both carotid arteries. At 22, 28, and 34 weeks after irradiation, blood samples were taken, and the arterial tree was removed for histological examination. Cholesterol levels in irradiated mice were not significantly different from age-matched controls, and markers of systemic inflammation (soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and C-reactive protein) were not …