Modest effect on plaque progression and vasodilatory function in atherosclerosis-prone mice exposed to nanosized TiO 2

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 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 2was 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 2had 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 2particles was associated with modest plaque progression in ApoE -/-mice. There were no associations between the pulmonary TiO 2exposure and inflammation or vasodilatory dysfunction. © 2011 Mikkelsen et al; licensee BioMed Central Ltd.