Modest vasomotor dysfunction induced by low doses of C(60 )fullerenes in apolipoprotein E knockout mice with different degree of atherosclerosis

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. C(60 )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 C(60 )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 C(60 )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 EC(50 )of sodium nitroprusside-induced vasorelaxation response in young apoE(-/- )mice. CONCLUSION: Treatment with C(60 )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 C(60 )fullerene treatment. These findings represent an important step in the hazard characterization of C(60 )fullerenes by showing that intraperitoneal administration is associated with a moderate decrease in the vascular function of mice with atherosclerosis.