Role of Myocardium-Derived Exosomal miRNAs in Doxorubicin-Induced Cardiomyopathy

Background: Doxorubicin-induced cardiomyopathy (DCM) remains a major clinical challenge, highlighting the need for early diagnostic biomarkers. Exosomal miRNAs have emerged as promising candidates because of their stability and regulatory roles in cardiovascular diseases. Methods: Exosomes were isolated from myocardial tissue samples of DOX-treated and control rats using differential ultracentrifugation and were subsequently characterized by transmission electron microscopy (TEM), Western blotting, and nanoparticle tracking analysis (NTA). Differentially expressed miRNAs were screened by microarray analysis. The miRanda algorithm was used to predict target genes, followed by functional enrichment analysis. qRT‒PCR validated selected miRNAs and their target genes. Results: Doxorubicin administration induced significant cardiac dysfunction, characterized by decreased left ventricular ejection fraction (LVEF) and increased serum levels of cardiac biomarkers (cTnI, BNP, and CK-MB). Microarray profiling revealed 26 differentially expressed miRNAs, and KEGG enrichment analysis indicated enrichment in the MAPK signaling pathway. qRT‒PCR demonstrated upregulation of exosomal miR-182 and downregulation of Taok2 mRNA, a key MAPK gene. ROC analysis indicated the potential of exosomal miR-182 for DCM diagnosis. Conclusion: Exosomal miR-182 may serve as a diagnostic marker for DCM. Bioinformatic analyses predict its potential regulation of the MAPK pathway through Taok2 targeting, although this mechanistic relationship requires experimental validation. These findings provide new perspectives for the early monitoring of DCM.