Sex-Specific Effects of Prenatal and Early Life Inorganic and Methylated Arsenic Exposure on Atherosclerotic Plaque Development and Composition in Adult A p o E - / - Mice.

Autor: Negro Silva LF; Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada., Makhani K; Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada., Lemaire M; Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada., Lemarié CA; Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada.; EA3878, European University of Occidental Brittany, Brest, France.; UMR 1078, Institut national de la santé et de la recherché médicale, Brest, France., Plourde D; Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada., Bolt AM; Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada., Chiavatti C; Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada., Bohle DS; Department of Chemistry, McGill University, Montreal, Quebec, Canada., Lehoux S; Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada., Goldberg MS; Department of Medicine, McGill University, Montreal, Quebec, Canada.; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada.; Division of Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada., Mann KK; Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada.
Jazyk: angličtina
Zdroj: Environmental health perspectives [Environ Health Perspect] 2021 May; Vol. 129 (5), pp. 57008. Date of Electronic Publication: 2021 May 17.
DOI: 10.1289/EHP8171
Abstrakt: Background: Epidemiologic studies indicate that early life arsenic exposures are linked to an increased risk of cardiovascular diseases. Different oxidation and methylation states of arsenic exist in the environment and are formed in vivo via the action of arsenic ( + 3 oxidation state) methyltransferase (As3MT). Methylated arsenicals are pro-atherogenic postnatally, but pre- and perinatal effects are unclear. This is particularly important because methylated arsenicals are known to cross the placenta.
Objectives: We tested the effects of early life exposure to inorganic and methylated arsenicals on atherosclerotic plaque formation and its composition in apolipoprotein E knock-out ( apoE - / - ) mice and evaluated whether apoE - / - mice lacking As3MT expression were susceptible to this effect.
Methods: We exposed apoE - / - or apoE - / - / As 3 MT - / - mice to 200  ppb inorganic or methylated arsenic in the drinking water from conception to weaning and assessed atherosclerotic plaques in the offspring at 18 wk of age. Mixed regression models were used to estimate the mean difference in each outcome relative to controls, adjusting for sex and including a random effects term to account for within-litter clustering.
Results: Early life exposure to inorganic arsenic, and more profoundly methylated arsenicals, resulted in significantly larger plaques in the aortic arch and sinus in both sexes. Lipid levels in these plaques were higher without a substantial difference in macrophage numbers. Smooth muscle cell content was not altered, but collagen content was lower. Importantly, there were sex-specific differences in these observations, where males had higher lipids and lower collagen in the plaque, but females did not. In mice lacking As3MT, arsenic did not alter the plaque size, although the size was highly variable. In addition, control apoE - / - / As 3 MT - / - mice had significantly larger plaque size compared with control apoE - / - .
Conclusion: This study shows that early life exposure to inorganic and methylated arsenicals is pro-atherogenic with sex-specific differences in plaque composition and a potential role for As3MT in mice. https://doi.org/10.1289/EHP8171.
Databáze: MEDLINE
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