Mechanism of Nano-Microplastics Exposure-Induced Myocardial Fibrosis: DKK3-Mediated Mitophagy Dysfunction and Pyroptosis

Abstract

Nano-microplastics (NMPs), as environmental pollutants, are widely present in nature and pose potential threats to biological health. This study aims to investigate the mechanisms by which NMPs inhibit mitophagy through the suppression of dickkopf-related protein 3 (DKK3) expression, leading to NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome-mediated cardiomyocyte pyroptosis and promoting myocardial fibrosis. Healthy adult male C57BL/6 mice were administered NMP solution via gavage, and their cardiac function was monitored. The results showed that NMP exposure significantly reduced left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) and increased the extent of myocardial fibrosis. Transcriptome sequencing identified 14 differentially expressed genes (DEGs), including MYL7. Using the random forest algorithm and functional enrichment analysis, DKK3 was identified as a key gene. In Vitro experiments further confirmed that NMPs downregulate DKK3 expression, thereby inhibiting mitophagy and promoting cardiomyocyte pyroptosis. This study elucidates the molecular mechanisms by which NMPs induce myocardial fibrosis and provides new theoretical bases and molecular targets for the diagnosis and treatment of heart diseases.