PM2.5 induces autophagy and apoptosis through endoplasmic reticulum stress in human endothelial cells.

Endothelial cells integrally form a crucial interface that maintains homeostasis of the cardiovascular system. As a vulnerable target of PM2.5, the underlying mechanisms of endothelial cell damage have yet to be fully elucidated. In the current study, two types of cell death, including autophagy and apoptosis, and an important organelle of the endoplasmic reticulum (ER) were focalized following PM2.5 exposure. As a result, the internalization of PM2.5 has the ability to induce excess ER stress, which is a crucial step for further autophagy and apoptosis in human endothelial cells, as confirmed by the pre-treatment with the inhibitor of ER stress (4-PBA) which effectively mitigates the apoptosis rate and LC3II expression. Intriguingly, crosstalk between ER stress and autophagy demonstrated that ER stress is probably involved in autophagic events, whereas autophagy has no significant effect on ER stress but confer a protective role against PM2.5-induced endothelial cell apoptosis. Moreover, PM2.5 results in blockage of autophagic flux (failed fusion between autophagosomes and lysosomes), which is detrimental to endothelial cell survival. In conclusion, our findings provide a valuable insight into the relation between autophagy and apoptosis under PM2.5-induced ER stress conditions, where the interplay between them ultimately determines cell fate.