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Ferroptosis involved in inhaled polystyrene microplastics leaded myocardial fibrosis through HIF-ROS-SLC7A11/GPX4 Pathway

Journal of Environmental Sciences 2025 6 citations ? Citation count from OpenAlex, updated daily. May differ slightly from the publisher's own count.
Danyang Huang, Huiwen Kang, Ziyan Liu, Wei Zhang, Jingyu Wang, Ziyan Wang, Guangyu Jiang, Ai Gao

Summary

Researchers found that inhaling polystyrene microplastics caused heart muscle scarring (fibrosis) in mice through a process called ferroptosis, a type of iron-dependent cell death. The microplastics triggered a chain reaction involving low oxygen signals and oxidative stress that depleted the heart cells' protective antioxidant systems. This study reveals a specific mechanism by which breathing in airborne microplastics could lead to lasting heart damage.

Polymers
Models
Study Type In vivo

The issue of microplastic (MPs) pollution has received increased attention in recent years. Studies have indicated that inhalation of microplastics may result in the cardiovascular harm. However, the specific mechanism remains to be elucidated. In this study, 5 µm polystyrene microplastics (PS-MPs) were employed to construct in vivo and in vitro exposure models to investigate the potential mechanisms of microplastic-induced cardiac fibrosis. In vivo model of respiratory exposure to MPs, echocardiography observed a decrease in systolic-diastolic function of the mouse heart, and myocardial tissue showed significant mitochondrial morphological abnormalities and myocardial fibrosis. In vitro models also revealed upregulation of fibrosis indicators in human cardiomyocytes AC16 cells. Transcriptome and RT-qPCR assay exposed that ferroptosis-related pathways were significantly gathered in the MPs group, with decreased expression of ferroptosis related genes SLC7A11 and GPX4. Liproxstatin-1 (Lip-1), a ferroptosis inhibitor, significantly ameliorated MPs-induced cardiomyocyte fibrosis and ferroptosis. We further demonstrated that inhibition of hypoxia-inducible factor α (HIF-α) and oxidative stress ameliorated PS-MPs-induced cardiomyocyte ferroptosis, and thus upregulation of the HIF pathway and oxidative stress may be the upstream mechanism of MPs-induced ferroptosis in myocardial fibrosis. Above all, our study demonstrated that MPs exposure resulted in cardiac fibrosis via the HIF-ROS-SLC7A11/GPX4 signaling pathway.

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