Dissection of the potential mechanism of polystyrene microplastic exposure on cardiomyocytes

Microplastics (MPs) are ubiquitous in the global biosphere, have widespread contact with humans, and increase exposure risks. Increasing evidence indicates that MPs exposure increases the risks of cardiovascular disease, however, a comprehensive exploration of the fundamental cellular mechanisms has yet to be undertaken. In this study, we used AC16 cells as a model and exposed them to 10 to 50 μg/mL of polystyrene MPs (PS-MPs), chosen based on the average daily intake and absorption of MPs by humans, to investigate their roles and mechanisms in cell injury. Proteomic analysis reveals that PS-MP-induced differentially expressed genes were enriched on endoplasmic reticulum (ER) stress and autophagy-related entries. The findings from immunofluorescence and western blotting provided further verification of the activation of ER stress by PS-MPs. Although the expression of LC3-II, a canonical autophagy marker was increased, PS-MPs inhibited autophagic flux instead of inducing autophagy. Importantly, ER stress not only contributes to PS-MPs-induced cell injury but also involved in PS-MPs-induced autophagic flux inhibition. Furthermore, the inhibition of autophagy, and the partial restoration of cell injury induced by PS-MPs was achieved through the activation of autophagy. Overall, the results reveal that activation of ER stress and inhibition of autophagic flux plays a significant role in the cell injury caused by PS-MPs in human cardiomyocytes, offering a novel perspective on the mechanism behind MPs-induced cardiomyocyte toxicity.