Arsenic-induced decreases in the vascular matrix.

Abstract:

: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.

journal_name

Toxicol Pathol

journal_title

Toxicologic pathology

authors

Hays AM,Lantz RC,Rodgers LS,Sollome JJ,Vaillancourt RR,Andrew AS,Hamilton JW,Camenisch TD

doi

10.1177/0192623308323919

subject

Has Abstract

pub_date

2008-10-01 00:00:00

pages

805-17

issue

6

eissn

0192-6233

issn

1533-1601

pii

0192623308323919

journal_volume

36

pub_type

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