For instance, Kumar S. et al. demonstrated that adventitial fibroblasts activated by pulmonary hypertension could release complement proteins through paracrine secretion of extracellular vesicles, subsequently reprogramming macrophage metabolism.50 Under neoplastic condition, studies have showed that chemotherapy can enhance extracellular vesicle release of complement proteins in breast cancer models and paradoxically increase the risk of lung metastasis51, 52. Here, VTN is linked to breast cancer.