Exposure to Diesel Exhaust Up-Regulates iNOS Expression in ApoE Knockout Mice

Details

• Personal Author:
  Bai N ; Kaufman JD ; Kavanagh TJ ; Kido T ; Rosenfeld ME ; van Breemen C ; van Eeden SF
• Description:
  Traffic related particulate matter air pollution is a risk factor for cardiovascular events; however, the biological mechanisms are unclear. We hypothesize that diesel exhaust (DE) inhalation induces up-regulation of inducible nitric oxide synthase (iNOS), which is known to contribute to vascular dysfunction, progression of atherosclerosis and ultimately cardiovascular morbidity and mortality. Methods: ApoE knockout mice (30-week) were exposed to DE (at 200 ug/m3 of particulate matter) or filtered-air (control) for 7 weeks (6 h/day, 5 days/week). iNOS expression in the blood vessels and heart was evaluated by immunohistochemistry and western blotting analysis. To examine iNOS activity, thoracic aortae were mounted in a wire myograph, and vasoconstriction stimulated by phenylephrine (PE) was measured with and without the presence of the specific inhibitor for iNOS (1400 W). NF-kB (p65) activity was examined by ELISA. The mRNA expression of iNOS and NF-kB (p65) was determined by real-time PCR. Results: DE exposure significantly enhanced iNOS expression in the thoracic aorta (4-fold) and heart (1.5 fold). DE exposure significantly attenuated PE-stimulated vasoconstriction by approximately 20%, which was partly reversed by 1400 W. The mRNA expression of iNOS and NF-kB was significantly augmented after DE exposure. NF-kB activity was enhanced 2-fold after DE inhalation, and the augmented NF-kB activity was positively correlated with iNOS expression (R2 = 0.5998). Conclusions: We show that exposure to DE increases iNOS expression and activity possibly via NF-kB-mediated pathway. We suspect that DE exposure-caused up-regulation of iNOS contributes to vascular dysfunction and atherogenesis, which could ultimately lead to urban air pollution-associated cardiovascular morbidity and mortality. [Description provided by NIOSH]
• Subjects:
  Air Pollution Animals Cardiovascular Diseases Cardiovascular System Occupational Health Particulate Matter Safety
• Keywords:
  Air Pollution Animal Studies ApoE Knockout Mice Atherosclerosis Author Keywords: Diesel Exhaust Cardiovascular Disease Diesel Exhaust Health Effects INOS NF-kB Oxidative Stress Particulates

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• ISSN:
  0041-008X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 10 ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  184-192
• Volume:
  255
• Issue:
  2
• NIOSHTIC Number:
  nn:20054954
• Citation:
  Toxicol Appl Pharmacol 2011 Sep; 255(2):184-192
• Contact Point Address:
  Stephan F. van Eeden, The James Hogg Research Centre, Providence Heart and Lung Institute, St. Paul's Hospital, University of British Columbia, 1081 Burrard Street, Vancouver, BC, Canada, V6Z1Y6
• Email:
  Stephan.vanEeden@hli.ubc.ca
• Federal Fiscal Year:
  2011
• Performing Organization:
  University of Washington
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Toxicology and Applied Pharmacology
• End Date:
  20250630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5ecd7935f454904f1a45f1cdd58c92583a60d916b8def6eb5fe7cb74913c928aecae5e1262b1dccd9ba4f2a1f3ed069467d1756f4e2649e2e80c18d45439de61
• Download URL:
  https://stacks.cdc.gov/view/cdc/217360/cdc_217360_DS1.pdf
• File Type:
  [PDF - 1.49 MB ]