Abstract
Chronic ingestion of arsenic is associated with an increased incidence of 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). At 5 and 8 weeks, RNA from the lungs of control and AsIII exposed animals was processed for microarray analysis. 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 a decrease in ECM gene transcripts in arsenic exposed hearts and in NIH3T3 fibroblasts incubated with arsenic. We also detected a disruption in the collagen and elastin within the ECM surrounding blood vessels of AsIII exposed mice. Immunohistochemical detection of α‐smooth muscle actin in blood vessel walls was also decreased in the AsIII exposed animals. These observations suggest an early pathological event in arsenic‐induced vasculopathies, specifically a disorganization of the extravascular matrix. Our data reveal a functional link between AsIII exposure and disruption in the vascular ECM.Supported by HL077493 and T32HL07249
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