Polystyrene nanoplastics exacerbate lipopolysaccharide-induced myocardial fibrosis and autophagy in mice via ROS/TGF-β1/Smad

Polystyrene nanoplastics (PS NPs) contamination is a serious problem for human and animal health. Excessive exposure to PS NPs can affect the structure and function of the heart. And lipopolysaccharide (LPS) induces myocardial damage, leading to myocardial fibrosis (MF). To investigate whether PS NPs exacerbate LPS-induced myocardial autophagy and fibrosis, we established in vivo and in vitro models of PS NPs/LPS exposure alone and in combination. We found that PS NPs/LPS exposure disrupts myocardial structure, significantly increases reactive oxygen species (ROS), triggers oxidative stress, promotes TGF-beta 1/Smad pathway activation, and leads to elevated levels of fibrotic proteins and collagen. Meanwhile, activation of AMPK/mTOR/ULK1 signaling pathway induced autophagy onset, and combined exposure of PS NPs/LPS exacerbated MF and autophagy. H9C2 cells were used for in vitro experiments, and the experimental results showed that the addition of TGF-beta receptor inhibitor LY2109761 to the exposed group not only inhibited the upregulation of fibrotic genes but also effectively reduced the expression of autophagic signals, indicating that combined exposure of PS NPs and LPS mediates and regulates cardiac autophagy through TGF-beta 1. The above results suggest that PS NPs exacerbate LPSinduced MF and autophagy in mice via ROS/TGF-beta 1/Smad. Our study provides some new evidence to clarify the potential mechanisms of PS NPs-induced cardiotoxicity.

Automated summary

Polystyrene nanoplastics (PS NPs) contamination has been identified as a serious health issue for humans and animals. This study found that combined exposure to PS NPs and lipopolysaccharide (LPS) exacerbated myocardial fibrosis and autophagy. The exposure disrupted myocardial structure, increased reactive oxygen species (ROS), triggered oxidative stress, and promoted the production of fibrotic proteins and collagen.