Arsenic-induced decreases in the vascular matrix.
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 alpha-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.
Hays
Allison M
AM
Department of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona 85721-0207, USA. hays@email.arizona.edu
Lantz
R Clark
RC
Rodgers
Laurel S
LS
Sollome
James J
JJ
Vaillancourt
Richard R
RR
Andrew
Angeline S
AS
Hamilton
Joshua W
JW
Camenisch
Todd D
TD
D000818:Animals; D001151:Arsenic / Q000633:toxicity; D018053:Arsenites / Q000008:administration & dosage / Q000633:toxicity*; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000235:genetics; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D004549:Elastin / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000235:genetics; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology*; D041681:NIH 3T3 Cells; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017670:Sodium Compounds / Q000008:administration & dosage / Q000633:toxicity*
D018053:Arsenites; D016326:Extracellular Matrix Proteins; D006360:Heat-Shock Proteins; D017670:Sodium Compounds; C017947:sodium arsenite; D003094:Collagen; D004549:Elastin; D001151:Arsenic