Fine particulate matter promoted vascular calcification through the miR-27b-5p/HES1 signaling pathway.

Fine particulate matter (PM2.5) remains to be the leading cause of global disease burden and is linked to arterial calcification in humans. This study revealed that PM2.5 facilitated the phenotype switching of mouse aortic smooth muscle (MOVAS) cells and promoted in vitro calcification in the present of phosphate calcification medium. Mechanistic investigations revealed that PM2.5 may inhibit the transcription of miR-27b-5p in an XBP1 dependent manner, which subsequently promoted the interaction of HES1 and Runx2, eventually leading to the osteogenic transformation of MOVAS cells. More importantly, through using human induced pluripotent stem cells (hiPSCs)-derived 3D blood vessel organoids to simulate PM2.5-induced effects on the vascular system, we also observed that PM2.5 enhanced the expression of osteogenic markers, while pretreatment with miR-27b-5p mimics could significantly attenuate the phenotype switching of VSMCs and calcium deposition in the organoids. The proposed mechanisms were also confirmed by a mouse model, in which PM2.5 could promote vascular calcification, increase intima-media thickness, and interfere with vascular function in both dosage and duration-dependent manners. In summary, this study comprehensively evaluated PM2.5-induced vascular calcification and unraveled implicated mechanisms, highlighting the importance of consistent efforts in reducing PM2.5 pollution and identifying sensitive cardiovascular biomarkers.