MiR-421 mediates PM2.5-induced endothelial dysfunction via crosstalk between bronchial epithelial and endothelial cells.

Abstract

Objective: PM_2.5 is closely linked to vascular endothelial injury and has emerged as a major threat to human health. Our previous research indicated that exposure to PM_2.5 induced an increased release of miR-421 from the bronchial epithelium. However, the role of miR-421 in PM_2.5-induced endothelial injury remains elusive.

Materials and methods: We utilized a subacute PM_2.5-exposure model in mice in vivo and an acute injury cell model in vitro to simulate PM_2.5-associated endothelial injury. We also used quantitative real-time polymerase chain reaction, western blot, enzyme-linked immunosorbent assay, and immunohistochemistry to investigate the role of miR-421 in PM_2.5-induced endothelial injury.

Results: Our findings reveal that inhibition of miR-421 attenuated PM_2.5-induced endothelial injury and hypertension. Mechanistically, miR-421 inhibited the expression of angiotensin-converting enzyme 2 (ACE2) in human umbilical vein endothelial cells and upregulated the expression of the downstream molecule inducible nitric oxide synthase (iNOS), thereby exacerbating PM_2.5-induced endothelial injury.

Conclusions: Our results indicate that PM_2.5 exposure facilitates crosstalk between bronchial epithelial and endothelial cells via miR-421/ACE2/iNOS signaling pathway, mediating endothelial damage and hypertension. MiR-421 inhibition may offer a new strategy for the prevention and treatment of PM_2.5-induced vascular endothelial injury.