Pulmonary exposure to carbon black nanoparticles and vascular effects.
BACKGROUND
Exposure to small size particulates is regarded as a risk factor for cardiovascular diseases.


METHODS
We exposed young and aged apolipoprotein E knockout mice (apoE-/-) to carbon black (Printex 90, 14 nm) by intratracheal instillation, with different dosing and timing, and measured vasomotor function, progression of atherosclerotic plaques, and VCAM-1, ICAM-1, and 3-nitrotyrosine in blood vessels. The mRNA expression of VCAM-1, ICAM-1, HO-1, and MCP-1 was examined in lung tissue.


RESULTS
Young apoE-/- mice exposed to two consecutive 0.5 mg/kg doses of carbon black exhibited lower acetylcholine-induced vasorelaxation in aorta segments mounted in myographs, whereas single doses of 0.05-2.7 mg/kg produced no such effects. The phenylephrine-dependent vasocontraction response was shifted toward a lower responsiveness in the mice exposed once to a low dose for 24 hours. No effects were seen on the progression of atherosclerotic plaques in the aged apoE-/- mice or on the expression of VCAM-1 and ICAM-1 and the presence of 3-nitrotyrosine in the vascular tissue of either young or aged apoE-/- mice. The expression of MCP-1 mRNA was increased in the lungs of young apoE-/- mice exposed to 0.9-2.7 mg/kg carbon black for 24 hours and of aged apoE-/- mice exposed to two consecutive 0.5 mg/kg doses of carbon black seven and five weeks prior to sacrifice.


CONCLUSIONS
Exposure to nano-sized carbon black particles is associated with modest vasomotor impairment, which is associated neither with nitrosative stress nor with any obvious increases in the expression of cell adhesion proteins on endothelial cells or in plaque progression. Evidence of pulmonary inflammation was observed, but only in animals exposed to higher doses.
Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark.
Lise K
LK
Vesterdal
Janne K
JK
Folkmann
Nicklas R
NR
Jacobsen
Majid
M
Sheykhzade
Håkan
H
Wallin
Steffen
S
Loft
Peter
P
Møller
D000280:Administration, Inhalation; D000375:Aging; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001992:Bronchoalveolar Lavage Fluid; D018932:Chemokine CCL2 / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D053758:Nanoparticles; D018384:Oxidative Stress; D058226:Plaque, Atherosclerotic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism; D053260:Soot / Q000633:toxicity*; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D001057:Apolipoproteins E; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D053260:Soot; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C002744:3-nitrotyrosine; D014443:Tyrosine; D051547:Heme Oxygenase-1