Toxicol Sci. 2011 Apr 21. [Epub ahead of print]
Lemaire M, Lemarié CA, Molina MF, Schiffrin EL, Lehoux S, Mann KK.
Lady Davis Institute for Medical Research, Dept. Oncology, McGill University, Montreal, H3T 1E2, Canada.
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 pro-atherogenic molecular changes, including decreased LXR target gene expression and increased pro-inflammatory cytokines. Significantly, our observations suggest that chronic moderate arsenic exposure may be a greater cardiovascular health risk than previously anticipated.
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