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Arsenic-Induced Decreases in the Vascular Matrix
1 Department of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona, USA Correspondence: Allison M. Hays, Ph.D., University of Arizona College of Pharmacy, P.O. Box 210207, Tucson, AZ 85721-0207, USA; e-mail:hays{at}email.arizona.edu.
Chronic ingestion of arsenic is associated with increased incidence of respiratory and cardiovascular diseases. To investigate the role of arsenic in early events in vascular pathology, C57BL/6 mice ingested drinking water with or without 50 ppb sodium arsenite (AsIII) for four, five, or eight weeks. At five and eight weeks, RNA from the lungs of control and AsIII-exposed animals was processed for microarray. Sixty-five genes were significantly and differentially expressed. Differential expression of extracellular matrix (ECM) gene transcripts was particularly compelling, as 91% of genes in this category, including elastin and collagen, were significantly decreased. In additional experiments, real-time RT-PCR showed an AsIII-induced decrease in many of these ECM gene transcripts in the heart and NIH3T3 fibroblast cells. Histological stains for collagen and elastin show a distinct disruption in the ECM surrounding small arteries in the heart and lung of AsIII-exposed mice. Immunohistochemical detection of
Key Words: arsenic • cardiovascular system • environmental toxicology • microarray • genomics • immunohistochemistry • lung • vascular system Abbreviations: Alas-1, aminolevulinate acid synthase • AsIII, sodium arsenite • BFD, blackfoot disease • Col1a1, collagen 1a1 • Col1a2, collagen 1a2 • Col6a3, collagen 6a3 • Col6a2, collagen 6a2 • Col3a1, collagen 3a1 • Col4a1, collagen 4a1 • Eln, elastin • Fbn1, fibrillin-1 • Fbln1, fibulin-1 • Fn1, fibronectin 1 • GST, glutathione-S-transferase • Has2, hyaluronan acid synthase-2 • Lox1, lysyl oxidase 1 • Lum, lumican • Mfap5, microfibrillar associated protein 5 • ppb, parts per billion • redox, reduction-oxidation • RMA, Robust MultiChip Analysis • SAM, Statistical Analysis of Microarrays
This version was published on October
1, 2008 Toxicologic Pathology, Vol. 36, No. 6,
805-817 (2008) This article has been cited by other articles:
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-smooth muscle actin in blood vessel walls was decreased in the AsIII-exposed animals. These data reveal a functional link between AsIII exposure and disruption in the vascular ECM. These AsIII-induced early pathological events may predispose humans to respiratory and cardiovascular diseases linked to chronic low-dose AsIII exposure. 
