Research

Modest vasomotor dysfunction induced by low doses of C₆₀ fullerenes in apolipoprotein E knockout mice with different degree of atherosclerosis

Lise K Vesterdal¹, Janne K Folkmann¹, Nicklas R Jacobsen², Majid Sheykhzade³, Håkan Wallin², Steffen Loft¹ and Peter Møller^1*

• * Corresponding author: Peter Møller pemo@pubhealth.ku.dk

Author Affiliations

¹ Department of Public Health, Section of Environment Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark

² Danish Research Centre for the Working Environment, Lersø Parkallé 105, DK-2100 Copenhagen Ø, Denmark

³ Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark

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Particle and Fibre Toxicology 2009, 6:5 doi:10.1186/1743-8977-6-5

Published: 25 February 2009

Abstract

Background

Exposure to small size particulate matter in urban air is regarded as a risk factor for cardiovascular effects, whereas there is little information about the impact on the cardiovascular system by exposure to pure carbonaceous materials in the nano-size range. C₆₀ fullerenes are nano-sized particles that are expected to have a widespread use, including cosmetics and medicines.

Methods

We investigated the association between intraperitoneal injection of pristine C₆₀ fullerenes and vasomotor dysfunction in the aorta of 11–13 and 40–42 weeks old apolipoprotein E knockout mice (apoE^-/-) with different degree of atherosclerosis.

Results

The aged apoE^-/-mice had lower endothelium-dependent vasorelaxation elicited by acetylcholine in aorta segments mounted in myographs and the phenylephrine-dependent vasoconstriction response was increased. One hour after an intraperitoneal injection of 0.05 or 0.5 mg/kg of C₆₀ fullerenes, the young apoE^-/- mice had slightly reduced maximal endothelium-dependent vasorelaxation. A similar tendency was observed in the old apoE^-/- mice. Hampered endothelium-independent vasorelaxation was also observed as slightly increased EC₅₀ of sodium nitroprusside-induced vasorelaxation response in young apoE^-/- mice.

Conclusion

Treatment with C₆₀ fullerenes affected mainly the response to vasorelaxation in young apoE^-/- mice, whereas the vasomotor dysfunction in old apoE^-/- mice with more advanced atherosclerosis was less affected by acute C₆₀ fullerene treatment. These findings represent an important step in the hazard characterization of C₆₀ fullerenes by showing that intraperitoneal administration is associated with a moderate decrease in the vascular function of mice with atherosclerosis.