ToxSci Advance Access originally published online on November 17, 2008
Toxicological Sciences 2009 107(2):312-323; doi:10.1093/toxsci/kfn236
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arsenic and Cardiovascular Disease
,1,
* Department of Pharmacology and Toxicology
Center for Environmental Genomics and Integrative Biology
Institute of Molecular Cardiology, University of Louisville, Louisville, Kentucky 40292
Departments of Environmental Medicine and Medicine, New York University School of Medicine, New York, New York 10016
¶ Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15219
1 To whom correspondence should be addressed at Department of Pharmacology & Toxicology, University of Louisville, 570 South Preston Street, Suite 221, Lousiville, KY 40202. Fax: (502) 852-2492. E-mail: jcstates{at}louisville.edu.
Received August 22, 2008; accepted November 5, 2008
 |
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.
Key Words: arsenic; inflammation; oxidative signaling; vascular disease; nutrition; microarray.