Title: Arsenic and cardiovascular disease.
Authors: States, J Christopher; Srivastava, Sanjay; Chen, Yu; Barchowsky, Aaron
Published In Toxicol Sci, (2009 Feb)
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.
PubMed ID: 19015167
MeSH Terms: Animals; Apolipoproteins E/genetics; Arsenic Poisoning/epidemiology; Arsenic Poisoning/genetics; Arsenic Poisoning/pathology*; Arsenic Poisoning/urine; Arsenic/toxicity*; Arsenic/urine; Atherosclerosis/chemically induced; Atherosclerosis/genetics; Atherosclerosis/pathology; Cardiovascular Diseases/epidemiology; Cardiovascular Diseases/genetics; Cardiovascular Diseases/pathology*; Cardiovascular Diseases/urine; Endoplasmic Reticulum/drug effects; Endoplasmic Reticulum/pathology; Environmental Exposure; Hemodynamics/drug effects; Humans; Mice; Mice, Knockout; Oxidative Stress/genetics; Oxidative Stress/physiology; Vasculitis/chemically induced; Vasculitis/genetics; Vasculitis/pathology