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

Abstract：

UNLABELLED: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 μg/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-κB (p65) activity was examined by ELISA. The mRNA expression of iNOS and NF-κB (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 ~20%, which was partly reversed by 1400 W. The mRNA expression of iNOS and NF-κB was significantly augmented after DE exposure. NF-κB activity was enhanced 2-fold after DE inhalation, and the augmented NF-κB 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-κB-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.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Bai N,Kido T,Kavanagh TJ,Kaufman JD,Rosenfeld ME,van Breemen C,van Eeden SF

doi

10.1016/j.taap.2011.06.013

subject

Has Abstract

pub_date

2011-09-01 00:00:00

pages

184-92

issue

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(11)00235-3

journal_volume

255

pub_type

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