Modest vasomotor dysfunction induced by low doses of C<sub>60 </sub>fullerenes in apolipoprotein E knockout mice with different degree of atherosclerosis

oleh: Loft Steffen, Wallin Håkan, Sheykhzade Majid, Jacobsen Nicklas R, Folkmann Janne K, Vesterdal Lise K, Møller Peter

Format: Article
Diterbitkan: BMC 2009-02-01

Deskripsi

<p>Abstract</p> <p>Background</p> <p>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<sub>60 </sub>fullerenes are nano-sized particles that are expected to have a widespread use, including cosmetics and medicines.</p> <p>Methods</p> <p>We investigated the association between intraperitoneal injection of pristine C<sub>60 </sub>fullerenes and vasomotor dysfunction in the aorta of 11–13 and 40–42 weeks old apolipoprotein E knockout mice (apoE<sup>-/-</sup>) with different degree of atherosclerosis.</p> <p>Results</p> <p>The aged apoE<sup>-/-</sup>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<sub>60 </sub>fullerenes, the young apoE<sup>-/- </sup>mice had slightly reduced maximal endothelium-dependent vasorelaxation. A similar tendency was observed in the old apoE<sup>-/- </sup>mice. Hampered endothelium-independent vasorelaxation was also observed as slightly increased EC<sub>50 </sub>of sodium nitroprusside-induced vasorelaxation response in young apoE<sup>-/- </sup>mice.</p> <p>Conclusion</p> <p>Treatment with C<sub>60 </sub>fullerenes affected mainly the response to vasorelaxation in young apoE<sup>-/- </sup>mice, whereas the vasomotor dysfunction in old apoE<sup>-/- </sup>mice with more advanced atherosclerosis was less affected by acute C<sub>60 </sub>fullerene treatment. These findings represent an important step in the hazard characterization of C<sub>60 </sub>fullerenes by showing that intraperitoneal administration is associated with a moderate decrease in the vascular function of mice with atherosclerosis.</p>