Modest effect on plaque progression and vasodilatory function in atherosclerosis-prone mice exposed to nanosized TiO2
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ABSTRACT: 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 TiO2. ApoE-/- mice were intratracheally instilled (0.5 mg/kg bodyweight) with rutile fine TiO2 (fTiO2, 288 nm), photocatalytic 92/8 anatase/rutile TiO2 (pTiO2, 12 nm), or rutile nano TiO2 (nTiO2, 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 TiO2 (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. TiO2-induced alterations in nitric oxide (NO) production were assessed in human umbilical vein endothelial cells (HUVECs). RESULTS: The exposure to nTiO2 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 TiO2 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 nTiO2. CONCLUSION: Repeated exposure to nanosized TiO2 particles was associated with modest plaque progression in ApoE-/- mice. There were no associations between the pulmonary TiO2 exposure and inflammation or vasodilatory dysfunction.
|Journal||Particle and Fibre Toxicology|
|Publication status||Published - 10 Nov 2011|
- Former Faculty of Pharmaceutical Sciences