Heterogeneity and Clinical Translation of Cardiac-Derived Extracellular Vesicles in Heart Failure: From Mechanisms to...

Heart failure (HF) represents a class of cardiovascular diseases that poses a serious threat to global health. Although current pharmacological and device-based therapies have exhibited some progress, significant challenges remain, including suboptimal treatment responses and the inability to effectively halt disease progression. Extracellular vesicles (EVs) are nanoscale membranous particles actively secreted by cells, which are capable of transporting bioactive molecules such as nucleic acids and proteins to mediate intercellular communication. Owing to the broad cellular origins and excellent biocompatibility of EVs, these particles offer extensive therapeutic potential. This review systematically elaborates on the key aspects of EVs, including the core molecular composition of these particles, as well as the biogenesis pathways and functional regulatory mechanisms involved. We further dissect the functional heterogeneity of EVs derived from cardiomyocytes, cardiac fibroblasts, endothelial cells, and immune cells in HF, highlighting the dual roles of EVs in either promoting or counteracting disease progression via cargo-dependent mechanisms. Additionally, we explore the translational applications of EVs in the diagnosis and treatment of HF, covering EV isolation, characterization, and scalable production strategies. The potential use of EVs as biomarkers, as well as the precision engineering of EVs for targeted clinical therapy, are also critically discussed.