Endothelial Heterogeneity in Pulmonary Hypertension

The lung endothelium is essential for maintaining normal lung structure and plays a key role in gas exchange, barrier function, angiogenesis, vascular tone, and inflammation regulation. The advent of single-cell RNA sequencing has revealed the unique heterogeneity of pulmonary endothelial cells (ECs) in their function, morphology, and localization. Pulmonary hypertension (PH) is a progressive vascular disorder marked by elevated pulmonary arterial pressure and vascular remodeling. Central to its pathogenesis is EC dysfunction, and emerging evidence highlights EC heterogeneity in driving the complexity of PH. The distinct lung endothelial subpopulations exhibit diverse molecular signatures and functional responses under PH. A complete picture of how these different subpopulations contribute to vascular remodeling of PH is critical to identify novel therapeutic opportunities. This brief review summarizes recent insights into EC dysfunction in PH, focusing on the role of specialized EC subsets and novel therapeutic strategies targeting EC dysfunction. We highlight the integration of cutting-edge technologies in understanding how endothelial heterogeneity shapes the trajectory of PH and opens new avenues for future therapeutic innovations.