Ambient air particulate matter exposure and tissue factor expression in atherosclerosis

Inhal Toxicol. 2008 Jan;20(2):127-37. doi: 10.1080/08958370701821482.

Abstract

Recent studies have suggested a link between inhaled particulate matter (PM) exposure and atherogenesis. We investigated tissue factor (TF) expression with ambient fine particulate matter (diameter < 2.5 microm, PM(2.5)) exposure and in response to in vitro exposure to fine and ultrafine PM in cultured human bronchial epithelial cells, vascular smooth muscle cells (hSMCs), and monocytes. ApoE-/- mice, fed with normal chow (NC) or high-fat chow (HFC), were exposed to concentrated PM(2.5) or filtered air (FA) for 6 mo (6 h/day, 5 day/wk, n = 28). Following in vivo ultrasound bio-microscopy (UBM) assessment of plaque area, macrophage infiltration (CD68) and TF expression in the aorta were quantified. Cultured cells were incubated with size-fractionated PM from cascade impactors, or with standard reference PM material (SRM, number 1649a) and assayed for TF protein, mRNA, and activity. UBM-derived plaque areas were 7 +/- 1% larger in the PM(2.5)-HFC than the FA-HFC group (p = .04), but not significantly different between the PM(2.5)-NC and FA-NC groups (p = .07). Immunohistochemistry revealed increased TF (15 +/- 3% vs. 8 +/- 2%, p < .01) and macrophage infiltration (19 +/- 2% vs. 14 +/- 3%, p < .01) in the plaques of PM(2.5)-HFC compared with FA-HFC groups. Impactor-collected PM(2.5) and ultrafine particles consistently increased TF protein in bronchial epithelial cells, monocytes, and hSMCs. TF mRNA expression increased rapidly (within 1 h) in response to SRM PM. We conclude that in vivo and in vitro exposure to ambient air PM(2.5) induces TF expression.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Air Pollution / adverse effects*
  • Animals
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Atherosclerosis / diagnostic imaging
  • Atherosclerosis / etiology
  • Atherosclerosis / metabolism*
  • Bronchi / drug effects
  • Bronchi / metabolism
  • Bronchi / pathology
  • Cells, Cultured
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Environmental Exposure / adverse effects*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Gene Expression Regulation / drug effects
  • Gene Silencing
  • Humans
  • Image Processing, Computer-Assisted
  • Inhalation Exposure
  • Male
  • Mice
  • Mice, Knockout
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Monocytes / pathology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • Particulate Matter / adverse effects*
  • RNA, Messenger / metabolism
  • Thromboplastin / genetics
  • Thromboplastin / metabolism*
  • Ultrasonography

Substances

  • Apolipoproteins E
  • Particulate Matter
  • RNA, Messenger
  • Thromboplastin