The effects of direct and macrophage-mediated exposure to aqueous fine particulate matter on vascular endothelial...

Fine particulate matter (PM_2.5) is an independent risk factor for vascular diseases. In this context, activated macrophages release inflammatory molecules that can contribute to endothelial dysfunction. While the effects of PM_2.5's solid fraction on vascular endothelial cells are well-documented, the effect of its polar compounds circulating in the bloodstream remains unclear. In this study, we examined the effects of direct and indirect (macrophage-mediated) exposure to aqueous PM_2.5 on the endothelium. CF-1 mice received intranasal instillations of PM_2.5 (30 μg in 10 μL) or saline, 5 days per week for two weeks. These animals exhibited considerable endothelial dysfunction linked to oxidative stress. Similarly, macrophages (RAW264.7 lineage) exposed to aqueous PM_2.5 (10-fold dilution) exhibited oxidative stress and inflammation, indicating that their reactive phenotype may contribute to the outcomes observed in vivo. Interestingly, their conditioned medium (10 % v/v) enhanced endothelial cell function (EOMA lineage) by reducing reactive oxygen species (ROS) production and promoting an endothelial nitric oxide synthase (eNOS)-dependent increase in nitrite levels, with the exact opposite effect observed in cells directly exposed to aqueous PM_2.5. These findings suggest that the macrophage secretome, rather than residual metals, may be responsible for these effects. Consistent with these findings, incubation with the animals' plasma (1 % v/v) also stimulated nitrite production. Additionally, caveolin-1, a key mediator of vesicle uptake, was overexpressed in endothelial cells exposed to conditioned medium, suggesting its involvement in monocyte-endothelium crosstalk. Finally, our results indicated that the macrophage secretome might serve as a mild stimulus, activating protective mechanisms in endothelial cells, whereas direct exposure to aqueous PM_2.5 induces dysfunction.