Archives of Toxicology

, Volume 80, Issue 3, pp 154–162 | Cite as

Induction of oxidative stress and inhibition of plasminogen activator inhibitor-1 production in endothelial cells following exposure to organic extracts of diesel exhaust particles and urban fine particles

  • Akiko Furuyama
  • Seishiro Hirano
  • Eiko Koike
  • Takahiro Kobayashi
Organ Toxicity and Mechanisms


Endothelial cells play important roles in anticoagulant and fibrinolytic systems. Recent studies suggest that increases in ambient particulate matter (PM) levels have been associated with an increase in mortality rate from cardiovascular diseases. We examined the production of heme oxygenase-1 (HO-1) and factors related to the fibrinolytic function by rat heart microvessel endothelial cells exposed to organic extracts of diesel exhaust particles (OE-DEP) and urban fine particles (OE-UFP) to investigate the direct effects of these soluble organic fractions in these PM on the fibrinolytic function of endothelial cells. The cell monolayer exposed to 10 μg/ml OE-DEP produced a larger amount of HO-1 than cells exposed to 10 μg/ml OE-UFP. OE-DEP and OE-UFP exposure reduced plasminogen activator inhibitor-1 (PAI-1) production by the cells but did not affect the production of thrombomodulin, tissue-type plasminogen activator, or urokinase-type plasminogen activator. Increased PAI-1 synthesis in response to treatment with 1.0 ng/ml tumor necrosis factor-α or 0.5 ng/ml transforming growth factor-β1 was reduced by OE-DEP exposure. Suppression of PAI-1 production by OE-DEP exposure was mediated through oxidative stress and was independent of HO-1 activity. These results suggest that exposure to the soluble organic fraction of PM and DEP induced oxidative stress and reduced the PAI-1 production of endothelial cells.


Heme oxygenase-1 PAI-1 Fibrinolysis TGF-β1 TNF-α 



We thank Dr. Tadao Suzuki and Dr. Toru Nakajima of the Japan Automobile Research Institute for OE-UFP preparation.


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Akiko Furuyama
    • 1
  • Seishiro Hirano
    • 2
  • Eiko Koike
    • 1
  • Takahiro Kobayashi
    • 1
    • 2
  1. 1.Inhalation toxicology Team, PM2.5 & DEP Research ProjectNational Institute for Environmental StudiesTsukubaJapan
  2. 2.Environmental Health Sciences DivisionNational Institute for Environmental StudiesTsukubaJapan

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