Distinct endothelial cells in chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition characterized by unresolved thrombi obstructing the pulmonary arteries. Endothelial cells (ECs) are essential regulators of thrombosis and thrombus resolution, yet their molecular phenotypes in CTEPH are incompletely understood. Using single-cell RNA sequencing of CTEPH surgical specimens and control ECs from the Human Lung Cell Atlas, we uncover marked EC heterogeneity in CTEPH. Compared to controls, CTEPH ECs display marked phenotypic shifts, with the loss and emergence of distinct EC subpopulations, including a unique subset co-expressing pulmonary and bronchial EC markers. Our analysis reveals perturbed endothelial thrombosis regulation, encompassing coagulation, fibrinolysis, inflammation, TGF-β signaling, and angiogenesis, while identifying novel target genes. These findings provide a comprehensive view of endothelial contributions to delayed thrombus resolution, offering new insights into the pathophysiology of CTEPH and potential therapeutic targets.