title: Ionizing radiation accelerates the development of atherosclerotic lesions in ApoE-/- mice and predisposes to an inflammatory plaque phenotype prone to hemorrhage.
abstract: 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 elevated. The lesions in irradiated arteries were macrophage rich, with a remarkable influx of inflammatory cells, predominantly granulocytes. Intraplaque hemorrhage and erythrocyte-containing macrophages were seen only in lesions of irradiated arteries. Based on these data, we propose that irradiation accelerates the development of macrophage-rich, inflammatory atherosclerotic lesions prone to intraplaque hemorrhage.
authors.affiliation: Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands. f.stewart@nki.nl
authors.forename: Fiona Anne
authors.initials: FA
authors.lastname: Stewart
authors.forename: Sylvia
authors.initials: S
authors.lastname: Heeneman
authors.forename: Johannes
authors.initials: J
authors.lastname: Te Poele
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Kruse
authors.forename: Nicola S
authors.initials: NS
authors.lastname: Russell
authors.forename: Marion
authors.initials: M
authors.lastname: Gijbels
authors.forename: Mat
authors.initials: M
authors.lastname: Daemen
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology*; D001158:Arteries / Q000528:radiation effects; D050197:Atherosclerosis / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D004032:Diet; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism; D006470:Hemorrhage / Q000209:etiology*; D006720:Homozygote; D007249:Inflammation / Q000150:complications*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D011839:Radiation, Ionizing; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein; D002784:Cholesterol