Hypoxia Impairs Migration of Human Dermal Lymph Endothelial Cells: Implications for Lymphedema Pathogenesis

Introduction: Lymphedema, characterized by abnormal lymph circulation, is a chronic debilitating condition often associated with chronic inflammation and hypoxia in lymphedematous tissue. Previously, using videocapillaroscopy, we found that the severity of lymphedema damages vasa vasorum vessels on the surface of lymph vessels, significantly compromising the oxygen supply environment to lymph endothelial cells. While previous research has indicated the inhibitory effects of hypoxic conditions on the proliferation of human dermal lymph endothelial cells (HDLECs), the impact on HDLEC migration remains unclear. This study aims to investigate the migration ability of HDLECs under hypoxic conditions, shedding light on the potential mechanisms underlying lymphedema progression and offering insights into therapeutic strategies. Materials and Methods and Results: Purchased HDLECs were cultured under normoxic (2% O₂) and hypoxic (1% O₂) conditions. Migration assays were performed using a scratch assay to assess the migratory capabilities of HDLECs. The experiment monitored cell migration over a period of 6 hours. Experiments were performed in triplicate. HDLECs were cultured to full confluence before the scratch assay. The results revealed a significant reduction in HDLEC migration under hypoxic conditions compared to normoxic conditions after 6 hours (p < 0.001). This suggests that hypoxic environments directly impair HDLEC migration. Conclusion: Hypoxia negatively affects HDLEC migration, potentially exacerbating lymphedema. Protecting vasa vasorum may preserve HDLEC migration and lymphangiogenesis. Further exploration of hypoxia-HDLEC interactions is crucial for understanding lymphedema pathogenesis and developing therapies.