title: Modest effect on plaque progression and vasodilatory function in atherosclerosis-prone mice exposed to nanosized TiO(2).
abstract: BACKGROUND
  There is growing evidence that exposure to small size particulate matter increases the risk of developing cardiovascular disease.
  
  
  METHODS
  We investigated plaque progression and vasodilatory function in apolipoprotein E knockout (ApoE(-/-)) mice exposed to TiO(2). ApoE(-/-) mice were intratracheally instilled (0.5 mg/kg bodyweight) with rutile fine TiO2 (fTiO2, 288 nm), photocatalytic 92/8 anatase/rutile TiO(2) (pTiO(2), 12 nm), or rutile nano TiO(2) (nTiO(2), 21.6 nm) at 26 and 2 hours before measurement of vasodilatory function in aorta segments mounted in myographs. The progression of atherosclerotic plaques in aorta was assessed in mice exposed to nanosized TiO(2) (0.5 mg/kg bodyweight) once a week for 4 weeks. We measured mRNA levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue to assess pulmonary inflammation and vascular function. TiO(2)-induced alterations in nitric oxide (NO) production were assessed in human umbilical vein endothelial cells (HUVECs).
  
  
  RESULTS
  The exposure to nTiO(2) was associated with a modest increase in plaque progression in aorta, whereas there were unaltered vasodilatory function and expression levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue. The ApoE(-/-) mice exposed to fine and photocatalytic TiO(2) had unaltered vasodilatory function and lung tissue inflammatory gene expression. The unaltered NO-dependent vasodilatory function was supported by observations in HUVECs where the NO production was only increased by exposure to nTiO(2).
  
  
  CONCLUSIONS
  Repeated exposure to nanosized TiO(2) particles was associated with modest plaque progression in ApoE(-/-) mice. There were no associations between the pulmonary TiO(2) exposure and inflammation or vasodilatory dysfunction.
authors.affiliation: Department of Public Health, University of Copenhagen, 1014 Copenhagen K, Denmark.
authors.forename: Lone
authors.initials: L
authors.lastname: Mikkelsen
authors.forename: Majid
authors.initials: M
authors.lastname: Sheykhzade
authors.forename: Keld A
authors.initials: KA
authors.lastname: Jensen
authors.forename: Anne T
authors.initials: AT
authors.lastname: Saber
authors.forename: Nicklas R
authors.initials: NR
authors.lastname: Jacobsen
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallin
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
authors.forename: Peter
authors.initials: P
authors.lastname: Møller
mesh_terms: D000393:Air Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D050197:Atherosclerosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D015870:Gene Expression / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D053758:Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D014025:Titanium / Q000493:pharmacokinetics / Q000633:toxicity*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D000393:Air Pollutants; D015815:Cell Adhesion Molecules; D018925:Chemokines; D042461:Vascular Endothelial Growth Factor A; C009495:titanium dioxide; D014025:Titanium
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