Functional and metabolic characterization of endothelial cells in chronic thromboembolic pulmonary hypertension

Abstract

Pulmonary hypertension (PH) is a condition of increased blood pressure within the arteries of the lung (mPAP > 20mmHg) which affects approximately 1% of the global population. Chronic thromboembolic pulmonary hypertension (CTEPH), group 4 PH, is characterized by unresolved pulmonary emboli and pulmonary vascular remodeling of both occluded and non-occluded vessels. The general aim of this thesis was to improve the understanding of CTEPH pathophysiology by focusing on patient endothelial cell (EC) behaviour and function. For this purpose, we isolated ECs from vascular material collected at pulmonary endarterectomy in patients with CTEPH (referred to as CTEPH-EC) and validated them as an in vitro model for studying endothelial pathology in CTEPH. In conclusion, we identified several abnormalities in CTEPH-EC that could play a role in pathological mechanisms driving CTEPH-specific vascular changes. We described alterations in key processes such as angiogenesis and migration, oxidative stress, metabolism and inflammation. Each of these processes may represent targets for novel therapies or biomarkers.</p