Endothelial features along the pulmonary vascular tree in chronic thromboembolic pulmonary hypertension: distinctive or shared facets?

Background. Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of pulmonary embolism, characterised by organized fibro-thrombotic material that partially or fully obstructs large pulmonary arteries, microvasculopathy and enlargement of the bronchial systemic vessels. Although the underlying mechanisms of CTEPH remain unclear, deficient angiogenesis and altered pulmonary arterial endothelial cell (PAEC) function may contribute to disease progression. Although differences in histological features, shear stress and ischemia are observed along the pulmonary vascular tree, the potential contribution of PAEC phenotype and function to these different aspects remains unexplored. We consequently hypothesized that angiogenic capacities and endothelial barrier function could contribute to disparities of histological features observed along the pulmonary vascular tree. Methods. We therefore explored histological aspects of the pulmonary vascular tree using pulmonary arterial lesions collected at pulmonary endarterectomy (PEA). We focused on the angiogenic vascular endothelial growth factor (VEGF)-A/VEGF receptor-2 (VEGFR2) axis and collagen 15A1 (COL15A1), a potential marker of endothelial cells of the systemic circulation. In parallel, we investigated in vitro angiogenic properties and barrier function of PAECs isolated from large and segmental pulmonary arterial lesions. Results. Segmental pulmonary arterial lesions were abundantly recanalised by neovessels, paralleled by an enriched expression of VEGFR2. VEGF-A expression was more prominent in large pulmonary arterial lesions. However, we did not observe any significant difference in in vitro angiogenic capacities and barrier function of PAECs isolated from large and segmental pulmonary arterial lesions. Interestingly, we found the presence of endothelial cells (CD31+) expressing COL15A1, but also CD31+ cells which do not express COL15A1, suggesting that endothelial cells both from systemic and pulmonary circulation contribute to lesions recanalization. Conclusion. Despite different in situ angiogenic cues in VEGF-A/VEGFR2 axis between large and segmental pulmonary arterial lesions in CTEPH, in vitro angiogenic capacities and barrier function remain unchanged. ### Competing Interest Statement MD received financial support from the Belgian Association of Patients for Pulmonary Hypertension.