In utero arsenic exposure induces early onset of atherosclerosis in ApoE-/- mice.
Consumption of arsenic contaminated drinking water has been linked to higher rates of coronary disease, stroke, and peripheral arterial disease. Recent evidence suggests that early life exposures may play a significant role in the onset of chronic adult diseases. To investigate the potential for in utero arsenic exposure to accelerate the onset of cardiovascular disease we exposed pregnant ApoE-knockout (ApoE(-/-)) mice to arsenic in their drinking water and examined the aortic trees of their male offspring for evidence of early disease 10 and 16 weeks after birth. Mice were maintained on normal chow after weaning. ApoE(-/-) mice are a commonly used model for atherogenesis and spontaneously develop atherosclerotic disease. Mice exposed to arsenic in utero showed a >2-fold increase in lesion formation in the aortic roots as well as the aortic arch compared to control mice at both 10 and 16 weeks of age. The mice exposed to arsenic also had a 20-40% decrease in total triglycerides, but no change in total cholesterol, phospholipids and total abundance of VLDL or HDL particles. Subfractionation of VLDL particles showed a decrease in large VLDL particles. In addition, the arsenic-exposed mice showed a vasorelaxation defect in response to acetylcholine suggesting disturbance of endothelial cell signalling. These results indicate that in utero arsenic exposure induces an early onset of atherosclerosis in ApoE(-/-) mice without a hyperlipidemic diet and support the hypothesis that in utero arsenic exposure may be atherogenic in humans.
Srivastava
Sanjay
S
Department of Medicine, University of Louisville, Louisville, KY 40202, United States.
D'Souza
Stanley E
SE
Sen
Utpal
U
States
J Christopher
JC
D000109:Acetylcholine / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics*; D018053:Arsenites / Q000008:administration & dosage / Q000633:toxicity*; D050197:Atherosclerosis / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D066298:In Vitro Techniques; D008074:Lipoproteins / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010784:Photomicrography / Q000379:methods; D011189:Potassium Chloride / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017670:Sodium Compounds / Q000008:administration & dosage / Q000633:toxicity*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014886:Weaning
D001057:Apolipoproteins E; D018053:Arsenites; D004791:Enzyme Inhibitors; D008074:Lipoproteins; D020030:Nitric Oxide Donors; D017670:Sodium Compounds; D009599:Nitroprusside; D010656:Phenylephrine; C017947:sodium arsenite; D011189:Potassium Chloride; D000109:Acetylcholine