Adolescent exposure to polylactic acid microplastics causes cardiac fibrosis by promoting cardiomyocyte senescence

Population studies and animal experiments have indicated that exposure to microplastics (MPs) is closely related to adverse cardiovascular outcomes. However, as far as we know, all current studies on MPs-induced cardiotoxicity are limited to traditional petroleum-based plastics, and there is a blank for potential heart damage caused by 'bioplastics' made of polylactic acid (PLA) materials. This study investigated the cardiotoxicity of PLA-MPs in mice and its potential mechanism. Adolescent mice exposed to PLA-MPs for 28 days showed obvious cardiac developmental toxicity, manifested as disordered arrangement of myocardial cells, thinning of myocardial thickness and fibrosis. Further studies found that ferroptosis and senescence were observed in the hearts of adolescent mice exposed to PLA-MPs. In vitro, we used H9c2 cells to study the cellular internalization, senescence and ferroptosis effects of PLA-MPs. We found that PLA-MPs exposure increased the senescence characteristics of H9c2 cells, such as increased SA-β-Gal activity, up-regulated expression of senescence-associated proteins (p16, p21, γH2AX) and senescence-associated inflammatory factors. Moreover, we found that PLA-MPs caused ferroptosis in H9c2 cells with elevated ferrous iron. Subsequent studies found that Fer-1 inhibited ferroptosis signal and alleviated PLA-MPs-induced H9c2 cell senescence. In summary, our findings highlight the cardiotoxic effects of biodegradable PLA-MPs through ferroptosis and senescence pathways, and provide insights into the toxicological effects of biodegradable MPs on mammalian cardiovascular system capacity.