Arsenic and cardiovascular disease

J. Christopher States, Sanjay Srivastava, Yu Chen, Aaron Barchowsky

Research output: Contribution to journalReview article

Abstract

Chronic arsenic exposure is a worldwide health problem. Although arsenic-induced cancer has been widely studied, comparatively little attention has been paid to arsenic-induced vascular disease. Epidemiological studies have shown that chronic arsenic exposure is associated with increased morbidity and mortality from cardiovascular disease. In addition, studies suggest that susceptibility to arsenic-induced vascular disease may be modified by nutritional factors in addition to genetic factors. Recently, animal models for arsenic-induced atherosclerosis and liver sinusoidal endothelial cell dysfunction have been developed. Initial studies in these models show that arsenic exposure accelerates and exacerbates atherosclerosis in apolipoprotein E-knockout mice. Microarray studies of liver mRNA and micro-RNA abundance in mice exposed in utero suggest that a permanent state of stress is induced by the arsenic exposure. Furthermore, the livers of the arsenic-exposed mice have activated pathways involved in immune responses suggesting a pro-hyperinflammatory state. Arsenic exposure of mice after weaning shows a clear dose-response in the extent of disease exacerbation. In addition, increased inflammation in arterial wall is evident. In response to arsenic-stimulated oxidative signaling, liver sinusoidal endothelium differentiates into a continuous endothelium that limits nutrient exchange and waste elimination. Data suggest that nicotinamide adenine dinucleotide phosphate oxidase-derived superoxide or its derivatives are essential second messengers in the signaling pathway for arsenic-stimulated vessel remodeling. The recent findings provide future directions for research into the cardiovascular effects of arsenic exposure.

Original languageEnglish (US)
Pages (from-to)312-323
Number of pages12
JournalToxicological Sciences
Volume107
Issue number2
DOIs
StatePublished - Feb 5 2009

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Keywords

  • Arsenic
  • Inflammation
  • Microarray
  • Nutrition
  • Oxidative signaling
  • Vascular disease

ASJC Scopus subject areas

  • Toxicology

Cite this

States, J. C., Srivastava, S., Chen, Y., & Barchowsky, A. (2009). Arsenic and cardiovascular disease. Toxicological Sciences, 107(2), 312-323. https://doi.org/10.1093/toxsci/kfn236