TY - JOUR
T1 - Modest effect on plaque progression and vasodilatory function in atherosclerosis-prone mice exposed to nanosized TiO2
AU - Mikkelsen, Lone
AU - Sheykhzade, Majid
AU - Jensen, Keld A
AU - Saber, Anne T
AU - Jacobsen, Nicklas R.
AU - Vogel, Ulla Birgitte
AU - Wallin, Håkan
AU - Loft, Steffen
AU - Møller, Peter
PY - 2011/11/10
Y1 - 2011/11/10
N2 - Background: There is growing evidence that exposure to small size particulate matter increases the risk of developing cardiovascular disease.Methods: We investigated plaque progression and vasodilatory function in apolipoprotein E knockout (ApoE -/-) mice exposed to TiO 2. ApoE -/- mice were intratracheally instilled (0.5 mg/kg bodyweight) with rutile fine TiO 2 (fTiO 2, 288 nm), photocatalytic 92/8 anatase/rutile TiO 2 (pTiO 2, 12 nm), or rutile nano TiO 2 (nTiO 2, 21.6 nm) at 26 and 2 hours before measurement of vasodilatory function in aorta segments mounted in myographs. The progression of atherosclerotic plaques in aorta was assessed in mice exposed to nanosized TiO 2 (0.5 mg/kg bodyweight) once a week for 4 weeks. We measured mRNA levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue to assess pulmonary inflammation and vascular function. TiO 2-induced alterations in nitric oxide (NO) production were assessed in human umbilical vein endothelial cells (HUVECs).Results: The exposure to nTiO 2 was associated with a modest increase in plaque progression in aorta, whereas there were unaltered vasodilatory function and expression levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue. The ApoE -/- mice exposed to fine and photocatalytic TiO 2 had unaltered vasodilatory function and lung tissue inflammatory gene expression. The unaltered NO-dependent vasodilatory function was supported by observations in HUVECs where the NO production was only increased by exposure to nTiO 2.Conclusion: Repeated exposure to nanosized TiO 2 particles was associated with modest plaque progression in ApoE -/- mice. There were no associations between the pulmonary TiO 2 exposure and inflammation or vasodilatory dysfunction.
AB - Background: There is growing evidence that exposure to small size particulate matter increases the risk of developing cardiovascular disease.Methods: We investigated plaque progression and vasodilatory function in apolipoprotein E knockout (ApoE -/-) mice exposed to TiO 2. ApoE -/- mice were intratracheally instilled (0.5 mg/kg bodyweight) with rutile fine TiO 2 (fTiO 2, 288 nm), photocatalytic 92/8 anatase/rutile TiO 2 (pTiO 2, 12 nm), or rutile nano TiO 2 (nTiO 2, 21.6 nm) at 26 and 2 hours before measurement of vasodilatory function in aorta segments mounted in myographs. The progression of atherosclerotic plaques in aorta was assessed in mice exposed to nanosized TiO 2 (0.5 mg/kg bodyweight) once a week for 4 weeks. We measured mRNA levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue to assess pulmonary inflammation and vascular function. TiO 2-induced alterations in nitric oxide (NO) production were assessed in human umbilical vein endothelial cells (HUVECs).Results: The exposure to nTiO 2 was associated with a modest increase in plaque progression in aorta, whereas there were unaltered vasodilatory function and expression levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue. The ApoE -/- mice exposed to fine and photocatalytic TiO 2 had unaltered vasodilatory function and lung tissue inflammatory gene expression. The unaltered NO-dependent vasodilatory function was supported by observations in HUVECs where the NO production was only increased by exposure to nTiO 2.Conclusion: Repeated exposure to nanosized TiO 2 particles was associated with modest plaque progression in ApoE -/- mice. There were no associations between the pulmonary TiO 2 exposure and inflammation or vasodilatory dysfunction.
KW - Former Faculty of Pharmaceutical Sciences
U2 - 10.1186/1743-8977-8-32
DO - 10.1186/1743-8977-8-32
M3 - Journal article
C2 - 22074227
SN - 1743-8977
VL - 8
SP - 32
JO - Particle and Fibre Toxicology
JF - Particle and Fibre Toxicology
IS - 1
ER -
