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

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.