From Heterogeneity to Plasticity: Endothelial Dynamics in Lung Disease

Endothelial heterogeneity and plasticity play an important role in lung development, homeostasis, and pathology. In recent years, increasing evidence has demonstrated that endothelial dysfunction contributes to the progression of various lung diseases, such as ADRS, PF, PH, and lung developmental disorders. Therefore, targeting endothelial cells could hold promising therapeutic strategies for preventing disease development. Although significant advances in technology have revolutionized our understanding of endothelial heterogeneity and plasticity, effective and curative treatment options remain limited. Here, we discuss the molecular and functional diversity of lung endothelial cells and their critical role in maintaining lung homeostasis and in lung pathologies. We also briefly describe advanced technologies, such as single-cell RNA sequencing and spatial transcriptomics, to uncover complex cell communication and underlying mechanisms. Furthermore, this review will identify future research questions for developing therapeutic approaches targeting lung endothelial cells.