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

<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. C₆₀fullerenes 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 C₆₀fullerenes and vasomotor dysfunction in the aorta of 11–13 and 40–42 weeks old apolipoprotein E knockout mice (apoE^-/-) with different degree of atherosclerosis.</p> <p>Results</p> <p>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 C₆₀fullerenes, 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 EC₅₀of sodium nitroprusside-induced vasorelaxation response in young apoE^-/-mice.</p> <p>Conclusion</p> <p>Treatment with C₆₀fullerenes 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 C₆₀fullerene treatment. These findings represent an important step in the hazard characterization of C₆₀fullerenes by showing that intraperitoneal administration is associated with a moderate decrease in the vascular function of mice with atherosclerosis.</p

Pulmonary exposure to carbon black nanoparticles and vascular effects

<p>Abstract</p> <p>Background</p> <p>Exposure to small size particulates is regarded as a risk factor for cardiovascular diseases.</p> <p>Methods</p> <p>We exposed young and aged apolipoprotein E knockout mice (<it>apoE^-/-</it>) 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 <it>VCAM-1</it>, <it>ICAM-1</it>, <it>HO-1</it>, and <it>MCP-1 </it>was examined in lung tissue.</p> <p>Results</p> <p>Young <it>apoE^-/-</it>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 <it>apoE^-/-</it>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 <it>apoE^-/-</it>mice. The expression of <it>MCP-1 </it>mRNA was increased in the lungs of young <it>apoE^-/-</it>mice exposed to 0.9-2.7 mg/kg carbon black for 24 hours and of aged <it>apoE^-/-</it>mice exposed to two consecutive 0.5 mg/kg doses of carbon black seven and five weeks prior to sacrifice.</p> <p>Conclusion</p> <p>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.</p

Lack of acute phase response in the livers of mice exposed to diesel exhaust particles or carbon black by inhalation

<p>Abstract</p> <p>Background</p> <p>Epidemiologic and animal studies have shown that particulate air pollution is associated with increased risk of lung and cardiovascular diseases. Although the exact mechanisms by which particles induce cardiovascular diseases are not known, studies suggest involvement of systemic acute phase responses, including C-reactive protein (CRP) and serum amyloid A (SAA) in humans. In this study we test the hypothesis that diesel exhaust particles (DEP) – or carbon black (CB)-induced lung inflammation initiates an acute phase response in the liver.</p> <p>Results</p> <p>Mice were exposed to filtered air, 20 mg/m³DEP or CB by inhalation for 90 minutes/day for four consecutive days; we have previously shown that these mice exhibit pulmonary inflammation (Saber AT, Bornholdt J, Dybdahl M, Sharma AK, Loft S, Vogel U, Wallin H. Tumor necrosis factor is not required for particle-induced genotoxicity and pulmonary inflammation., Arch. Toxicol. 79 (2005) 177–182). As a positive control for the induction of an acute phase response, mice were exposed to 12.5 mg/kg of lipopolysaccharide (LPS) intraperitoneally. Quantitative real time RT-PCR was used to examine the hepatic mRNA expression of acute phase proteins, serum amyloid P (<it>Sap</it>) (the murine homologue of <it>Crp</it>) and <it>Saa1 </it>and <it>Saa3</it>. While significant increases in the hepatic expression of <it>Sap, Saa1 </it>and <it>Saa3 </it>were observed in response to LPS, their levels did not change in response to DEP or CB. In a comprehensive search for markers of an acute phase response, we analyzed liver tissue from these mice using high density DNA microarrays. Globally, 28 genes were found to be significantly differentially expressed in response to DEP or CB. The mRNA expression of three of the genes (serine (or cysteine) proteinase inhibitor, clade A, member 3C, apolipoprotein E and transmembrane emp24 domain containing 3) responded to both exposures. However, these changes were very subtle and were not confirmed by real time RT-PCR.</p> <p>Conclusion</p> <p>Our findings collectively suggest that <it>Sap, Saa1 </it>and <it>Saa3 </it>are not induced in livers of mice exposed to DEP or CB. Despite pulmonary inflammation in these mice, global transcriptional profiling of liver did not reveal any hepatic response following exposure by inhalation.</p