The main role of the lung is to support blood oxygenation while removing carbon dioxide from the body. Appropriate blood circulation through the lungs, ensured by pulmonary blood vessels (arteries, capillaries and veins), is therefore crucial to support this organ’s function. In the context of pulmonary arterial hypertension (PAH), a dramatic increase in blood pressure in the pulmonary blood vessels ultimately results in right heart hypertrophy (corresponding to an abnormal enlargement of the cardiac muscle of the right heart ventricle, which pumps the blood to the lung), and heart failure, responsible for patients’ death. This disease is associated with a dysfunction of lung endothelial cells (ECs), which compose the innermost layer of blood vessels and regulate several key functions, such as vascular tone, blood vessel permeability, inflammation, etc. In PAH, lung EC dysfunction promotes an intense pulmonary vascular remodeling, imbalanced vascular tone, and inflammation. To date, with the exception of lung transplantation, this rare disease remains incurable with limited survival. A better understanding of the lung vasculature and of molecular processes underlying this disease is therefore necessary to propose new effective therapies.
Since ECs are diverse in order to support different functions throughout the whole body and the lung vasculature, the main objective of this project was to provide an in-depth molecular characterization of the lung EC heterogeneity in health and disease, and highlight PAH-specific EC subtype(s) involved in vascular remodeling, if any. Since the host lab previously showed that EC metabolism is a cornerstone of EC function in health and disease, a second objective was to characterize the metabolic fingerprints of lung ECs and in particular of PAH-specific EC subtypes(s) associated with vascular remodeling.
