title: 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.
abstract: 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 microg/ml OE-DEP produced a larger amount of HO-1 than cells exposed to 10 microg/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-alpha or 0.5 ng/ml transforming growth factor-beta1 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.
authors.affiliation: Inhalation toxicology Team, PM2.5 & DEP Research Project, National Institute for Environmental Studies, 16-2 Onogawa, 305-8506 Tsukuba, Japan. kawagoe@nies.go.jp
authors.forename: Akiko
authors.initials: A
authors.lastname: Furuyama
authors.forename: Seishiro
authors.initials: S
authors.lastname: Hirano
authors.forename: Eiko
authors.initials: E
authors.lastname: Koike
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000187:drug effects / Q000235:genetics; D008954:Models, Biological; D009206:Myocardium / Q000166:cytology; D018384:Oxidative Stress; D010316:Particle Size; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis*; D051381:Rats; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D017395:Plasminogen Activator Inhibitor 1; D001335:Vehicle Emissions; D006419:Heme Oxygenase (Decyclizing)