Exposure to Diesel Exhaust Upregulates COX-2 Expression in ApoE Knockout Mice

Details

• Personal Author:
  Bai N ; Kaufman JD ; Kavanagh TJ ; Rosenfeld ME ; Tranfield EM ; van Eeden SF
• Description:
  Introduction: We have shown that diesel exhaust (DE) inhalation caused progression of atherosclerosis; however, the mechanisms are not fully understood. We hypothesize that exposure to DE upregulates cyclooxygenase (COX) expression and activity, which could play a role in DE-induced atherosclerosis. Methods: ApoE knockout mice (30-week old) fed with regular chow were exposed to DE (at 200 ug/m3 of particulate matter) or filtered air (control) for 7 weeks (6 h/day, 5 days/week). The protein and mRNA expression of COX-1 and COX-2 were evaluated by immunohistochemistry analysis and quantitative real-time PCR, respectively. To examine COX activity, thoracic aortae were mounted in a wire myograph, and phenylephrine (PE)-stimulated vasoconstriction was measured with and without the presence of COX antagonists (indomethacin). COX-2 activity was further assessed by urine 2,3-dinor-6-keto PGF1a level, a major metabolite of prostacyclin I2 (PGI2). Results: Immunohistochemistry analysis demonstrates that DE exposure enhanced COX-2 expression in both thoracic aorta (p < 0.01) and aortic root (p < 0.03), with no modification of COX-1 expression. The increased COX-2 expression was positively correlated with smooth muscle cell content in aortic lesions (R2 = 0.4081, p < 0.008). The fractional changes of maximal vasoconstriction in the presence of indomethacin was attenuated by 3-fold after DE exposure (p < 0.02). Urine 2,3-dinor-6-keto PGF1a level was 15-fold higher in DE group than the control (p < 0.007). The mRNA expression of COX-2 (p < 0.006) and PGI synthase (p < 0.02), but not COX-1, was significantly augmented after DE exposure. Conclusion: We show that DE inhalation enhanced COX-2 expression, which is also associated with phenotypic changes of aortic lesion. [Description provided by NIOSH]
• Subjects:
  Air Pollution Animals Cardiovascular Diseases Cardiovascular System Occupational Health Particulate Matter Safety
• Keywords:
  Air Pollution Animal Studies ApoE Knockout Mouse Atherosclerosis Author Keywords: Diesel Exhaust Cardiovascular Disease Cyclooxygenase Diesel Exhaust Health Effects Particulates
• ISSN:
  0895-8378
• 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
• Volume:
  24
• Issue:
  8
• NIOSHTIC Number:
  nn:20054984
• Citation:
  Inhal Toxicol 2012 Jul; 24(8):518-527
• Contact Point Address:
  Stephan van Eeden, MD, PhD, 1081 Burrard Street, Vancouver, BC, Canada, V6Z1Y6, The James Hogg Research Centre, Providence Heart and Lung Institute, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada
• Email:
  Stephan.vanEeden@hli.ubc.ca
• Federal Fiscal Year:
  2012
• Performing Organization:
  University of Washington
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Inhalation Toxicology
• End Date:
  20250630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:fc4f815d1fd0c685d1ab1de58c1e097992e622a0900c94b1e408333e0aa9a7e9be83c96fb5fbf414e0a432b13bcfa718c676db91a803db5bdc0613440b6061a5
• Download URL:
  https://stacks.cdc.gov/view/cdc/217389/cdc_217389_DS1.pdf
• File Type:
  [PDF - 1.21 MB ]