title: Chronic Internal Exposure to Low Dose 137Cs Induces Positive Impact on the Stability of Atherosclerotic Plaques by Reducing Inflammation in ApoE-/- Mice.
abstract: After Chernobyl and Fukushima Daï Chi, two major nuclear accidents, large amounts of radionuclides were released in the environment, mostly caesium 137 (137Cs). Populations living in contaminated territories are chronically exposed to radionuclides by ingestion of contaminated food. However, questions still remain regarding the effects of low dose ionizing radiation exposure on the development and progression of cardiovascular diseases. We therefore investigated the effects of a chronic internal exposure to 137Cs on atherosclerosis in predisposed ApoE-/- mice. Mice were exposed daily to 0, 4, 20 or 100 kBq/l 137Cs in drinking water, corresponding to range of concentrations found in contaminated territories, for 6 or 9 months. We evaluated plaque size and phenotype, inflammatory profile, and oxidative stress status in different experimental groups. Results did not show any differences in atherosclerosis progression between mice exposed to 137Cs and unexposed controls. However, 137Cs exposed mice developed more stable plaques with decreased macrophage content, associated with reduced aortic expression of pro-inflammatory factors (CRP, TNFα, MCP-1, IFNγ) and adhesion molecules (ICAM-1, VCAM-1 and E-selectin). Lesions of mice exposed to 137Cs were also characterized by enhanced collagen and smooth muscle cell content, concurrent with reduced matrix metalloproteinase MMP8 and MMP13 expression. These results suggest that low dose chronic exposure of 137Cs in ApoE-/- mice enhances atherosclerotic lesion stability by inhibiting pro-inflammatory cytokine and MMP production, resulting in collagen-rich plaques with greater smooth muscle cell and less macrophage content.
authors.affiliation: IRSN, Institut de Radioprotection et de Sûreté Nucléaire, Laboratoire de RadioToxicologie Experimentale, 92262, Fontenay-aux-Roses, France.
authors.forename: Clélia
authors.initials: C
authors.lastname: Le Gallic
authors.affiliation: IRSN, Institut de Radioprotection et de Sûreté Nucléaire, Laboratoire de RadioToxicologie Experimentale, 92262, Fontenay-aux-Roses, France.
authors.forename: Yohann
authors.initials: Y
authors.lastname: Phalente
authors.affiliation: IRSN, Institut de Radioprotection et de Sûreté Nucléaire, Laboratoire de RadioToxicologie Experimentale, 92262, Fontenay-aux-Roses, France.
authors.forename: Line
authors.initials: L
authors.lastname: Manens
authors.affiliation: IRSN, Institut de Radioprotection et de Sûreté Nucléaire, Laboratoire de RadioToxicologie Experimentale, 92262, Fontenay-aux-Roses, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dublineau
authors.affiliation: IRSN, Institut de Radioprotection et de Sûreté Nucléaire, Laboratoire de RadioToxicologie Experimentale, 92262, Fontenay-aux-Roses, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Benderitter
authors.affiliation: IRSN, Institut de Radioprotection et de Sûreté Nucléaire, Laboratoire de RadioToxicologie Experimentale, 92262, Fontenay-aux-Roses, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Gueguen
authors.affiliation: Lady Davis Institute, McGill University, Montreal, Canada.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lehoux
authors.affiliation: IRSN, Institut de Radioprotection et de Sûreté Nucléaire, Laboratoire de RadioToxicologie Experimentale, 92262, Fontenay-aux-Roses, France.
authors.forename: Teni G
authors.initials: TG
authors.lastname: Ebrahimian
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002588:Cesium Radioisotopes / Q000737:chemistry; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D005720:Gamma Rays; D018836:Inflammation Mediators / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D018384:Oxidative Stress / Q000528:radiation effects
chemical_list: D001057:Apolipoproteins E; D015815:Cell Adhesion Molecules; D002588:Cesium Radioisotopes; D016207:Cytokines; D018836:Inflammation Mediators; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D002784:Cholesterol; D020782:Matrix Metalloproteinases