Arsenic and cardiovascular disease.
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.
States
J Christopher
JC
Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky 40292, USA. jcstates@louisville.edu
Srivastava
Sanjay
S
Chen
Yu
Y
Barchowsky
Aaron
A
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001151:Arsenic / Q000633:toxicity* / Q000652:urine; D020261:Arsenic Poisoning / Q000453:epidemiology / Q000235:genetics / Q000473:pathology* / Q000652:urine; D050197:Atherosclerosis / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics / Q000473:pathology* / Q000652:urine; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000473:pathology; D004781:Environmental Exposure; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D014657:Vasculitis / Q000139:chemically induced / Q000235:genetics / Q000473:pathology
D001057:Apolipoproteins E; D001151:Arsenic