fig2

Figure 2. EV-mediated intercellular communication in DCM: pathological mechanisms and therapeutic opportunities. The diabetic milieu characterized by hyperglycemia and IR (center) alters EV release and cargo composition from cardiac cells. EVs function as mediators of communication among cardiomyocytes, endothelial cells, and fibroblasts, thereby regulating multiple pathological processes involved in DCM progression. The left (red) pathway illustrates the pathogenic effects of EVs derived from metabolically stressed cells. These EVs transfer pathological molecular signals, including validated EV-associated cargoes and EV-related regulatory molecules, including miR-320 (cardiomyocyte-derived), miR-130b-3p (adipocyte-derived) and MST1 (CMEC-derived), which promote oxidative stress, fibrosis, apoptosis, microvascular dysfunction, and metabolic impairment, ultimately contributing to cardiac remodeling and HF. The right (green) pathway highlights protective/therapeutic EVs derived from MSCs or engineered platforms. These approaches deliver or modulate cardioprotective molecular signals, including validated EV-associated cargoes and protective regulators, such as miR-21-5p (CPC-derived exosomes), which enhance metabolic homeostasis, preserve vascular function, attenuate fibrosis and apoptosis, and improve cardiac remodeling. The balance between pathogenic and protective EV signaling influences the progression or attenuation of diabetic cardiac injury. Red ↑ indicate upregulated; green ↓ indicate downregulated; Solid arrows indicate established direct interactions, whereas dashed arrows denote putative or indirect regulatory relationships that require further experimental validation. CPC: Cardiac progenitor cell; DCM: diabetic cardiomyopathy; EndMT: endothelial-to-mesenchymal transition; ER: endoplasmic reticulum; EVs: extracellular vesicles; HF: heart failure; IR: insulin resistance; miRNA: microRNA; MSCs: mesenchymal stem cells; MST1: macrophage stimulating 1; CMEC: cardiac microvascular endothelial cell.