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Arsenic exposure accelerates atherogenesis in apolipoprotein E(-/-) mice
Petia P Simeonova1, Tracy Hulderman, Dan Harki
1Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA. psimeonova@cdc.gov
Environmental Health Perspectives
|November 5, 2003
Summary
Elevated arsenic in drinking water significantly increases atherosclerosis in apolipoprotein E-deficient mice by accumulating in vessel walls and inducing inflammation. This suggests arsenic
Area of Science:
- Environmental Toxicology
- Cardiovascular Pathology
- Molecular Biology
Background:
- Epidemiologic studies link arsenic exposure to increased vascular disease risk.
- Arsenic's atherogenic potential requires further investigation in controlled models.
Purpose of the Study:
- To evaluate the atherogenic potential of arsenic using apolipoprotein E-deficient (ApoE) mice and in vitro vascular cell systems.
- To investigate the mechanisms underlying arsenic-induced vascular effects.
Main Methods:
- ApoE-deficient and wild-type mice were exposed to sodium arsenite in drinking water.
- In vitro studies utilized primary human aorta endothelial and smooth muscle cells.
- Assessed lesion size, serum cholesterol, arsenic accumulation in vessel walls, and gene expression.
Main Results:
- Arsenic exposure significantly increased aortic lesion size in ApoE-deficient mice, without raising serum cholesterol.
- Arsenic accumulated in the vessel wall and induced inflammatory gene expression (interleukin-8) in endothelial cells.
- No lesions were observed in arsenic-exposed wild-type mice.
Conclusions:
- Arsenic promotes atherosclerosis in a susceptible genetic background (ApoE deficiency) via mechanisms independent of hypercholesterolemia.
- Arsenic-induced endothelial inflammation may contribute to vascular damage.
- Arsenic in drinking water poses a significant risk for cardiovascular disease development.