Multi-omics approach to personalised treatment: insights into thrombus-derived exosome regulation in cardiomyocyte ferritinophagy

作者：Youfu He, Lin Ai, Yu Zhou, Jing Huang, Xiangshu Long, Qiang Wu · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1607355 · 被引用次数：9 · 研究领域：Ferroptosis and cancer prognosis、RNA modifications and cancer、Cancer-related molecular mechanisms research

Background: Type 1 myocardial infarction (T1MI) is an acute ischemic event triggered by the rupture of a coronary atherosclerotic plaque. The pathogenesis of T1MI is highly complex, involving disturbances in iron metabolism, cell apoptosis, immune activation, and inflammatory responses. In recent years, ferritinophagy, a novel autophagic mechanism regulating iron homeostasis, has attracted increasing attention for its role in cardiovascular diseases. However, its precise involvement in T1MI remains to be fully elucidated. This study aims to systematically analyse the mechanism of ferritinophagy in T1MI and explore its potential connection to immune and inflammatory responses. Methods: Exosomes were isolated from coronary thrombi of T1MI patients and subjected to comprehensive transcriptomic profiling. Differentially expressed lncRNAs and mRNAs were validated through functional assays, including RIP, FISH, ChIP, and m6A methylation experiments. Cardiomyocyte models and integrated bulk and single-cell RNA sequencing were used to clarify cellular context and regulatory networks, with particular emphasis on YTHDF family proteins. Bioinformatics analyses, including GO and KEGG, were employed for pathway annotation. Results: Electron microscopy confirmed the presence of exosomes in coronary thrombi. Thrombus-derived exosomes (TEs) induced pronounced ferritinophagy in cardiomyocytes, evidenced by increased autophagosomes, ROS, apoptosis, and iron overload, with these effects amelior...