Group 1 Idiopathic Pulmonary Arterial Hypertension (IPAH) and connective tissue disease-associated PAH (CTD-aPAH) and group 4 Chronic Thromboembolic Pulmonary Hypertension (CTEPH) are two of the five clinical diagnostic categories for Pulmonary Hypertension (PH). The disease PH is progressive, fatal, and incurable. Recent research has shown that aberrant metabolic processes in the endothelium may play a key part in the pathogenic mechanisms producing PH, but these pathways are still poorly understood. In order to examine intracellular metabolism, this study provides a novel method for analyzing PH endothelium function. It builds on the genome scale metabolic reconstruction of the EC. We show that, regardless of the PH diagnosis, the intracellular metabolic activities of ECs in PH patients cluster into four phenotypes. Notably, the clinical importance of the metabolic phenotypes is suggested by the large differences in illness severity amongst them. The PH phenotypes' considerable metabolic variations suggest that several treatment approaches may be necessary. Additionally, research into whether this creates a brand new field of precision medicine is necessary to enable their identification through diagnostic capacities.
