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Arsenic and cardiovascular disease.

J Christopher States1, Sanjay Srivastava, Yu Chen

  • 1Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky 40292, USA. jcstates@louisville.edu

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Chronic arsenic exposure harms cardiovascular health, accelerating atherosclerosis and increasing vascular inflammation. Research in animal models reveals arsenic

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Area of Science:

  • Environmental Health
  • Cardiovascular Toxicology
  • Vascular Biology

Background:

  • Chronic arsenic exposure is a global health concern, primarily linked to cancer.
  • Less is known about arsenic's impact on vascular disease, despite epidemiological links to cardiovascular morbidity and mortality.
  • Genetic and nutritional factors may influence susceptibility to arsenic-induced vascular conditions.

Purpose of the Study:

  • To investigate the mechanisms underlying arsenic-induced vascular disease using animal models.
  • To explore the effects of arsenic exposure on atherosclerosis and liver sinusoidal endothelial cell function.
  • To identify molecular pathways involved in arsenic's cardiovascular toxicity.

Main Methods:

  • Development and utilization of animal models for arsenic-induced atherosclerosis.
  • Analysis of liver mRNA and micro-RNA in mice exposed to arsenic in utero.
  • Assessment of inflammation in arterial walls and endothelial cell differentiation in response to arsenic.

Main Results:

  • Arsenic exposure accelerated and worsened atherosclerosis in apolipoprotein E-knockout mice.
  • In utero arsenic exposure induced a persistent stress state and pro-hyperinflammatory responses in the liver.
  • Arsenic exposure led to increased arterial inflammation and altered liver sinusoidal endothelium, with nicotinamide adenine dinucleotide phosphate oxidase-derived superoxide implicated in vessel remodeling.

Conclusions:

  • Chronic arsenic exposure significantly contributes to vascular disease, including atherosclerosis and endothelial dysfunction.
  • Arsenic exposure triggers inflammatory and oxidative stress pathways, leading to detrimental cardiovascular effects.
  • These findings highlight critical areas for future research on arsenic's cardiovascular toxicity and potential interventions.