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<p>Abstract</p> <p>Background</p> <p>There is growing evidence that exposure to small size particulate matter increases the risk of developing cardiovascular disease.</p> <p>Methods</p> <p>We investigated plaque progression and vasodilatory function in apolipoprotein E knockout (<it>ApoE</it>^-/-) mice exposed to TiO₂. <it>ApoE</it>^-/-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 <it>Mcp-1</it>, <it>Mip-2</it>, <it>Vcam-1</it>, <it>Icam-1 </it>and <it>Vegf </it>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).</p> <p>Results</p> <p>The exposure to nTiO₂was associated with a modest increase in plaque progression in aorta, whereas there were unaltered vasodilatory function and expression levels of <it>Mcp-1</it>, <it>Mip-2</it>, <it>Vcam-1</it>, <it>Icam-1 </it>and <it>Vegf </it>in lung tissue. The <it>ApoE^-/-</it>mice exposed to fine and photocatalytic TiO₂had 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.</p> <p>Conclusion</p> <p>Repeated exposure to nanosized TiO₂particles was associated with modest plaque progression in <it>ApoE^-/-</it>mice. There were no associations between the pulmonary TiO₂exposure and inflammation or vasodilatory dysfunction.</p>