A living cell quartz crystal microbalance biosensor for continuous monitoring of cytotoxic responses of macrophages to single-walled carbon nanotubes

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.