Neovascularization and angiogenic gene expression following chronic arsenic exposure in mice

Nicole V. Soucy, Debra Mayka, Linda R. Klei, Antonia A. Nemec, John A. Bauer, Aaron Barchowsky

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


Exposure to arsenic in drinking water increases incidence of cardiovascular diseases. However, the basic mechanisms and genetic changes that promote these diseases are unknown. This study investigated the effects of chronic arsenic exposure on vessel growth and expression of angiogenic and tissue remodeling genes in cardiac tissues. Male mice were exposed to low to moderately high levels of arsenite (AsIII) for 5, 10, or 20 wk in their drinking water. Vessel growth in Matrigel implants was tested during the last 2 wk of each exposure period. Implant vascularization increased in mice exposed to 5-500 ppb AsIII for 5 wk. Similar increases were seen following exposure to 50-250 ppb of AsIII over 20 wk, but the response to 500 ppb decreased with time. RT-PCR analysis of cardiac mRNA revealed differential expression of angiogenic or tissue remodeling genes, such as vascular endothelial cell growth factor (VEGF), VEGF receptors, plasminogen activator inhibitor-1, endothelin-1, and matrix metalloproteinase-9, which varied with time or amount of exposure. VEGF receptor mRNA and cardiac microvessel density were reduced by exposure to 500 ppb AsIII for 20 wk. These data demonstrate differential concentration and time-dependent effects of chronic arsenic exposure on cardiovascular phenotype and vascular remodeling that may explain the etiology for AsIII-induced disease.

Original languageEnglish
Pages (from-to)29-41
Number of pages13
JournalCardiovascular Toxicology
Issue number1
StatePublished - 2005

Bibliographical note

Funding Information:
This work was supported by the Superfund Basic Research Program (ES 07373) and the services of the Norris Cotton Cancer Center at Dartmouth Hitchcock Medical Center.


  • Angiogenesis
  • Arsenic
  • Endothelin-1
  • Matrigel
  • Matrix metalloproteinase-9
  • Neovascularization
  • Plasminogen activator inhibitor-1
  • Vascular endothelial cell growth factor

ASJC Scopus subject areas

  • Molecular Biology
  • Toxicology
  • Cardiology and Cardiovascular Medicine


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