| Arsenic exposure in drinking-water is a significant worldwide health problem. It causes adverse human health effects, such as cancer, increases the risks for others such as cardiovascular disease, and accelerates atherosclerosis. In this study, we analyze arsenic-induced gene expression changes in the liver of ApoE-knockout mice given 49 ppm arsenic in drinking-water. We hypothesize chronic arsenic exposure accelerates atherosclerosis by disrupting liver homeostasis, causing aberrant gene expression changes. Networks revealed hubs on 3 stress-response MAP kinase pathways, ERK, JNK, and p38. Pathways revealed mitochondrial dysfunction and oxidative phosphorylation enrichment from the gene set. Transcription factor binding site analysis revealed specific transcription factors Foxd1, estrogen receptors, heat shock factor, Myc, and Pparg. Taken together, results suggest metabolic function disruption in the mitochondria related to oxidative stress and increased MAPK activity. Future studies should focus on arsenic's effects on mitochondria dealing with metabolism and activation of ERK, JNK, and p38 MAPK pathways. |
