Exposure to diesel exhaust up-regulates iNOS expression in ApoE knockout mice

Journal Article · Thu Sep 01 00:00:00 EDT 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2011.06.013· OSTI ID:21587826

Ni, Bai ^[1]; Kido, Takashi ^[2]; Kavanagh, Terrance J; Kaufman, Joel D; Rosenfeld, Michael E ^[3]; Breemen, Cornelis van ^[1]; Eeden, Stephan F. van, ^[2]

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1. Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC (Canada)
2. James Hogg Research Centre, Providence Heart and Lung Institute, St. Paul's Hospital, University of British Columbia, Vancouver, BC (Canada)
3. Department of Occupational and Environmental Health, University of Washington, Seattle, WA (United States)

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 {mu}g/m{sup 3} 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-{kappa}B (p65) activity was examined by ELISA. The mRNA expression of iNOS and NF-{kappa}B (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 {approx} 20%, which was partly reversed by 1400 W. The mRNA expression of iNOS and NF-{kappa}B was significantly augmented after DE exposure. NF-{kappa}B activity was enhanced 2-fold after DE inhalation, and the augmented NF-{kappa}B activity was positively correlated with iNOS expression (R{sup 2} = 0.5998). Conclusions: We show that exposure to DE increases iNOS expression and activity possibly via NF-{kappa}B-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. - Highlights: > Exposed ApoE knockout mice (30-week) to diesel exhaust (DE) for 7 weeks. > Examine iNOS expression and activity in the blood vessels and heart. > DE exposure enhanced iNOS protein and mRNA expression in the aorta and heart. > iNOS activity was also increased after DE exposure. > This up-regulation of iNOS may contribute to vascular dysfunction and atherogenesis.

• OSTI ID: 21587826
• Journal Information: Toxicology and Applied Pharmacology, Vol. 255, Issue 2; Other Information: DOI: 10.1016/j.taap.2011.06.013; PII: S0041-008X(11)00235-3; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AIR POLLUTION
AORTA
ARTERIOSCLEROSIS
ENZYME IMMUNOASSAY
HAZARDS
HEART
HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE
INHALATION
KNOCK-OUT REACTIONS
LEUKOCYTES
LIPOPROTEINS
MACROPHAGES
MESSENGER-RNA
MICE
MORTALITY
NITRIC OXIDE
POLYMERASE CHAIN REACTION
VASOCONSTRICTION
ANIMAL CELLS
ANIMALS
ARTERIES
BIOASSAY
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD VESSELS
BODY
BODY FLUIDS
CARDIOVASCULAR DISEASES
CARDIOVASCULAR SYSTEM
CHALCOGENIDES
CONNECTIVE TISSUE CELLS
DIRECT REACTIONS
DISEASES
ENZYMES
GENE AMPLIFICATION
GLYCOSYL TRANSFERASES
IMMUNOASSAY
INTAKE
LIPIDS
MAMMALS
MATERIALS
NITROGEN COMPOUNDS
NITROGEN OXIDES
NUCLEAR REACTIONS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXIDES
OXYGEN COMPOUNDS
PENTOSYL TRANSFERASES
PHAGOCYTES
POLLUTION
PROTEINS
RNA
RODENTS
SOMATIC CELLS
TRANSFERASES
VASCULAR DISEASES
VERTEBRATES