Modest vasomotor dysfunction induced by low doses of C60 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 EC50 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.