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Prenatal arsenic exposure altered liver gene expression associated with accelerated atherosclerosis
Author(s) -
States J.Christopher,
Singh Amar V,
Miller Heather L,
Piao Yulan,
Ko Minoru S.H.,
Knudsen Thomas B
Publication year - 2008
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.22.1_supplement.1137.4
Subject(s) - offspring , arsenic , biology , gene expression , microrna , knockout mouse , gene , andrology , genetics , medicine , chemistry , pregnancy , organic chemistry
Offspring of ApoE‐knockout mice exposed to arsenic in drinking water while pregnant exhibit accelerated and exacerbated atherosclerosis. Microarray analyses of liver mRNAs and microRNAs were performed to investigate the potential role of altered liver development in arsenic induced atherosclerosis. Liver RNAs from newborn and 10 week old mice were analyzed. Principal component analysis indicated that developmental trajectory was altered by arsenic exposure. A 51 gene signature of mRNAs altered by arsenic exposure at both ages was obtained. Nodes of interaction identified by Pathway Architect within this gene set include HSPA8, IgM and HNF4A. DAVID analysis of the overlap of arsenic exposure‐altered mRNAs and putative targets of altered microRNAs suggested that gluconeogeneis and glycolysis pathways were suppressed in newborn mice and pathways for protein export, ribosome, antigen processing and presentation, and complement and coagulation cascades were induced in 10 week old mice. These results support the hypthesis that in utero arsenic exposure induces changes in liver development that may alter liver inflammatory responses contributing to athero accelerated atherosclerosis. (Supported by PHS grants R01ES011314 & P30ES014443, UofL Center for Genetics and Molecular Medicine pilot grant, UofL Collaborative Planning and Development Grant and Intramural Research Program of NIA/NIH)