Pulmonary Endothelial Extracellular Vesicles Preferentially Interact and Are Processed in Pulmonary Endothelial Cells

Extracellular vesicles (EVs) regulate vascular injury and homeostasis; however, the intracellular mechanisms for the EV effects are unknown. While EV components and functions are well studied, their cellular uptake and intracellular processing remain unclear. Following our previous work on EVs, we investigated EV uptake mechanisms and organelle localization. Pulmonary endothelial–derived EVs showed preferential interaction with pulmonary vessels, particularly injured vessels. Co‐culture experiments confirmed endothelial cells as exclusive EV targets via energy‐dependent, clathrin‐mediated endocytosis. Intracellularly, EVs colocalized with lysosomes and trans‐Golgi, suggesting degradation and protein recycling pathways. These findings provide insights into temporal EV uptake dynamics and organelle interactions, establishing a foundation for understanding EV processing and content distribution mechanisms.