Exosomes in remote ischemic preconditioning-mediated organ protection: Molecular mechanisms and therapeutic...

Remote ischemic preconditioning (RIPC) is an endogenous protective strategy that confers resistance against sustained ischemia-reperfusion injury in distant organs. RIPC induces protective responses through complex neuronal, humoral, and systemic signaling pathways. Increasing evidence suggests that exosomes may serve as important mediators of humoral inter-organ communication during RIPC. Exosomes are small extracellular vesicles released by donor cells that transport biologically active molecules, including lipids, proteins, messenger RNAs, and microRNAs, to recipient cells, thereby modulating cellular responses to injury. Emerging evidence indicates that RIPC-associated exosomes and their molecular cargo contribute to protection against ischemia-reperfusion injury in organs such as the heart, brain, kidney, and spinal cord. Several exosomal molecules, including miRNAs, HSP90, HIF-1α, and NOX2, have been implicated in the regulation of cellular pathways associated with inflammation, oxidative stress, apoptosis, mitochondrial function, and tissue survival. In particular, alterations in exosomal miRNAs and protein and metabolite profiles following RIPC suggest that exosomes may participate in the transmission of protective signals from remote ischemic tissues to target organs. The therapeutic potential of exosomes is further supported by their ability to transport multiple bioactive molecules and their potential application as biomarkers or delivery vehicles for therapeutic cargo. However, the specific exosomal components responsible for RIPC-mediated protection and their causal contribution to inter-organ signaling remain to be fully established. Therefore, the present review summarizes the emerging evidence on the role of exosomes in RIPC-mediated organ protection, with particular emphasis on cardiovascular and cerebral ischemia-reperfusion injury, the molecular cargo involved, underlying protective mechanisms, and their potential therapeutic and translational applications.