Advanced imaging techniques reveal differential spatial distribution of nano- and micro-particles explaining unequal effects on cardiovascular function – implications for air pollution health effects

Introduction: With the rise of urbanization and industrialization, humans are being exposed to increasing amounts of air pollution derived particulate matter (PM). PM is usually classified by its size into PM₁₀ (<10 µm), PM_2.5 (<2.5 µm) and PM_0.1 (<0.1 µm). These classifications are created for reporting environmental concentrations but the impact of different PM sizes on the lung and other remote organs is not fully elucidated. Here we used PM of different sizes with fluorescent label or MRI-active to observe organ distribution and damage in a mouse inhalation model.

Methods and Results: C57BL/6 mice were exposed to two types of PM, fluorescent styrene PM (size 0.2 µm and 2.0 µm) and magnetic iron oxide PM (size 0.25 µm and 4.00 µm, both silanized to prevent iron toxicity). Exposure was performed using a custom rodent exposure system from TSE Systems GmbH (Hochtaunuskreis, Germany). Body distribution of fluorescent PM was documented by IVIS imaging in the lung. The smaller PM (designated nano) showed less fluorescence then larger PM (designated micro), pointing to micro PM accumulation in the lung. Body distribution of magnetic PM was documented in the heart and liver by MRI. Nano PM showed slight tendency to accumulation in the heart and liver, but low amount of magnetic PM did not provide enough T2* contrast to obtain significant difference. In both fluorescent and magnetic PM the nano PM exposed mice had higher systolic blood pressure. Endothelial function was impaired in the isolated aortic rings of fluorescent nano PM exposed, but not micro PM exposed mice. Markers of oxidative stress and inflammation were more prominently elevated in the lung of micro PM, supporting the accumulation of micro PM in the lung. In the heart, aorta and cortex, nano PM exposure elevated the oxidative stress and inflammation markers, showing that nano PM was able to reach remote organs through the circulation. Immunohistochemical staining of the aortic sections points to increased oxidative stress and increase in endothelin-1 expression of nano PM exposed mice, corroborating the endothelial function findings.

Conclusion: Inhalation of micrometer sized PM resulted in the accumulation in the lung tissue and localized increase in oxidative stress and inflammation, while inhalation of nanometer sized PM resulted in penetration into the circulation initiating oxidative stress and inflammation in the vasculature and in the remote organ systems.