Extracellular vesicle-mediated communication in diabetic cardiomyopathy: cellular mechanisms, metabolic remodeling, and emerging therapeutic strategies

Abstract

Diabetic cardiomyopathy (DCM) is an increasingly recognized cardiac complication of diabetes and contributes substantially to diabetes-associated cardiovascular morbidity and mortality. Extracellular vesicles (EVs), particularly small EVs (sEVs), have emerged as critical mediators of intercellular communication by transferring diverse bioactive cargoes, including microRNAs (miRNAs), long non-coding RNAs, circular RNAs, and proteins. Although sEVs have frequently been referred to as “exosomes” in previous literature, their precise classification remains challenging because current methodologies cannot reliably distinguish endosome-derived vesicles from other EV populations. Accumulating evidence indicates that EV-associated cargoes, particularly miRNAs, participate in regulating key pathogenic processes in DCM, including cardiomyocyte injury, apoptosis, oxidative stress, inflammation, metabolic remodeling, and fibrosis. Although the field of EVs in DCM remains at an early stage, emerging findings have provided new insights into disease mechanisms and highlighted the potential utility of EVs as biomarkers and therapeutic platforms. This review summarizes recent advances in EV biology in DCM, with a focus on their roles in cellular communication networks, metabolic remodeling, and disease progression. We further discuss the translational potential of EV-based approaches, including their applications as diagnostic biomarkers, therapeutic targets, and delivery systems, while addressing current challenges related to EV heterogeneity, cargo specificity, and clinical implementation. A better understanding of EV-mediated signaling networks may facilitate the development of precision strategies for early detection, risk stratification, and targeted intervention in diabetic cardiac disease.