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Early onset of atherosclerosis in ApoE‐knockout mice is induced by in utero arsenic exposure
Author(s) -
States J. Christopher,
Srivastava Sanjay,
Sen Utpal,
D’Souza Stanley E.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a810-c
Subject(s) - in utero , offspring , endocrinology , medicine , apolipoprotein e , knockout mouse , sodium arsenite , arsenic , biology , chemistry , pregnancy , disease , fetus , genetics , receptor , organic chemistry
Chronic arsenic ingestion causes arterial disease. Developmental toxicant exposures may accelerate the onset of chronic adult diseases. We investigated whether in utero arsenic exposure accelerates onset of cardiovascular disease by exposing pregnant ApoE‐knockout mice to 49 ppm arsenic as sodium arsenite in their drinking water and examining aortic trees of their male offspring for evidence of disease 10 weeks after birth. Offspring mice were maintained on normal chow after weaning. Lesion formation in the aortic roots as well as the aortic arch in mice exposed to arsenic in utero was increased >2‐fold relative to control mice. Total plasma cholesterol, phospholipids and total abundance of VLDL or HDL particles were unchanged in arsenic‐exposed mice. However, arsenic exposed mice had a >40% decrease in total plasma triglycerides. Subfractionation of VLDL particles revealed a decrease in large VLDL particles. a vasorelaxation defect in response to acetylcholine in phenylepinephrine pre‐contracted aortic rings from arsenic exposed mice suggested disturbance of endothelial cell signaling. We conclude that in utero arsenic exposure induces an early onset of atherosclerosis in ApoE‐knockout mice without a hyperlipidemic diet and that in utero arsenic exposure may be atherogenic in humans. (Supported by PHS grants R01HL65618, R01ES011314, and a grant from UofL Center for Genetics and Molecular Medicine)