title: Exposure to moderate arsenic concentrations increases atherosclerosis in ApoE-/- mouse model.
abstract: Arsenic is a widespread environmental contaminant to which millions of people are exposed worldwide. Exposure to arsenic is epidemiologically linked to increased cardiovascular disease, such as atherosclerosis. However, the effects of moderate concentrations of arsenic on atherosclerosis formation are unknown. Therefore, we utilized an in vivo ApoE(-/-) mouse model to assess the effects of chronic moderate exposure to arsenic on plaque formation and composition in order to facilitate mechanistic investigations. Mice exposed to 200 ppb arsenic developed atherosclerotic lesions, a lower exposure than previously reported. In addition, arsenic modified the plaque content, rendering them potentially less stable and consequently, potentially more dangerous. Moreover, we observed that the lower exposure concentration was more atherogenic than the higher concentration. Arsenic-enhanced lesions correlated with several proatherogenic molecular changes, including decreased liver X receptor (LXR) target gene expression and increased proinflammatory cytokines. Significantly, our observations suggest that chronic moderate arsenic exposure may be a greater cardiovascular health risk than previously anticipated.
authors.affiliation: Deptartment of Oncology, Lady Davis Institute for Medical Research, McGill University, Montreal, QC, Canada.
authors.forename: Maryse
authors.initials: M
authors.lastname: Lemaire
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Lemarié
authors.forename: Manuel Flores
authors.initials: MF
authors.lastname: Molina
authors.forename: Ernesto L
authors.initials: EL
authors.lastname: Schiffrin
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lehoux
authors.forename: Koren K
authors.initials: KK
authors.lastname: Mann
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001151:Arsenic / Q000633:toxicity*; D050197:Atherosclerosis / Q000139:chemically induced* / Q000473:pathology*; D008076:Cholesterol, HDL / Q000097:blood; D016207:Cytokines / Q000032:analysis / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D005786:Gene Expression Regulation; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors
chemical_list: D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D016207:Cytokines; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D001151:Arsenic