Pulmonary hypertension – an explorative metabolomic analysis of the endothelium

Abstract Background Pulmonary hypertension (PH) is classified into five clinical diagnostic groups, including group 1 (idiopathic pulmonary arterial (IPAH) and connective tissue disease-associated PAH (CTD-aPAH)) 4 (chronic thromboembolic (CTEPH)). PH a progressive, life-threatening, incurable disease. The pathological mechanisms underlying remain elusive; recent evidence has revealed that abnormal metabolic activities in the endothelium may play crucial role. Purpose Introducing novel approach for studying endothelial function, building on genome-scale (GEM) reconstruction of cell (EC) to investigate intracellular metabolism. Methods This prospective observational study includes 35 patients with either or CTEPH. We have previously developed platform by reconstructing most comprehensive model (EC-GEM). Since EC direct contact blood flow, we can adjust EC-GEM measuring extracellular metabolites from calculating flux EC. conducted individual models, i.e., total different models. Additionally, each was widely analyzed; total, 190 were investigated. enables us develop heatmap at patient levels. Patients similar combined. Results Four distinct phenotypes identified; all independent classification PH. observed clinically relevant differences NT-pro BNP levels WHO functional between these phenotypes. Also, important cellular identified separating four Two characterized catabolic crisis extreme citric acid cycle turnover energy production. However, one also suffered oxidative stress. Conclusion In systems analysis correlated but diagnosis. finding enable identify therapeutic targets specific respective thus promote personalized medicine Funding Acknowledgement Type funding sources: Foundation. Main source(s): funded Novo Nordisk Foundation research grant NNF20OC0064556 Heart Center Research Council, Copenhagen University Hospital, Rigshospitalet, provided Jørn Carlsen