Particulate matter promotes vascular calcification via the regulation of miR-26a-5p-mediated autophagy in calcifying vascular cells and Apoe-/- mice.

Vascular calcification is hallmark of cardiovascular disease, which has a high morbidity and mortality. A growing body of evidence suggests that vascular calcification has been linked to particulate matter (PM2.5) exposure. However, the molecular mechanism of how PM2.5 promotes vascular calcification remains unclear. This study demonstrated that PM2.5 exposure promoted calcium phosphate deposition, accompanied by autophagy activation in calcifying vascular cells. Moreover, PM2.5 treatment upregulated autophagy-related proteins and aggravated calcium nodule formation in calcifying vascular cells. Bioinformatic prediction combined with dual-luciferase reporter assays verified that miR-26a-5p directly targeted the 3'UTR of ULK1. PM2.5 exposure markedly reduced endogenous miR-26a-5p abundance, which relieved transcriptional inhibition of ULK1 and elevated autophagy levels. Furthermore, PM2.5 exposure accelerated vascular calcification in Apoe-/- mice, whereas 3-MA (an autophagy inhibitor) significantly alleviated the promoting effect of PM2.5. Our study revealed a key mechanism that underlies PM2.5 exposure promoted vascular calcification, a process in which miR-26a-5p initiates ULK1-independent autophagy and plays a critical regulatory role. Taken together, these findings provide novel insights insights into the association between PM2.5 exposure and vascular calcification both in vitro and in vivo, and provides a theoretical basis for PM2.5-induced harmful health effects.