Exosomal microRNA in diabetic myocardial disorder: Mechanisms, diagnosis, and treatment

Exosomes are intracellular vesicles formed through the endocytic pathway, progressing from early endosome formation to late endosome maturation, multivesicular body generation, and fusion with the plasma membrane. MicroRNAs (miRs), key functional cargo of exosomes, regulate gene expression, the cell cycle, and organismal development. However, the significance of exosomal microRNAs (exo-miRs) in the diagnosis and treatment of diabetic myocardial disorder (DMD) remains controversial. Current evidence indicates that exo-miRs influence DMD through mechanisms involving glucose and lipid metabolism, endothelial cell injury, cardiomyocyte apoptosis, pyroptosis, hypertrophy, and myocardial fibrosis. For diagnosis, elevations in circulating miR-1, miR-130b-3p, and miR-133a, together with reductions in miR-19b-3p, miR-21, miR-126, and miR-181b-5p, have been identified as potential diagnostic markers for DMD, with miR-21 emerging as the most promising candidate. For therapeutic applications, exo-miRs derived from various cellular sources, including cardiomyocytes, cardiac fibroblasts, endothelial progenitor cells, mesenchymal and embryonic stem cells, adipocytes, hepatocytes, macrophages, muscle cells, and the extracellular matrix, exhibit potential in treating DMD. Notably, exo-miR-126 and exo-miR-146a, as well as their synthetic mimics, are currently considered the most promising therapeutic agents. By integrating evidence on exo-miRs from diverse cellular origins and emphasizing their diagnostic and therapeutic translational potential in DMD, this review provides new insights into precision medicine strategies for diabetic cardiac complications.