Fig. 7.

Pharmacological inhibition of glucose-6-phosphate dehydrogenase (G6PD) attenuated metabolic reprogramming in idiopathic pulmonary arterial hypertension (iPAH) smooth muscle cells (SMCs). A: metabolomic analysis indicates activation of the pentose phosphate pathway, accumulation of late Krebs cycle intermediates, and increase of one carbon metabolism in SMCs isolated and cultured from pulmonary arteries (PAs) of iPAH patients (red) as compared with non-iPAH individuals (control; blue). This phenotype is rescued by inhibition of G6PD with NEOU (1 μM; green) treatment for 48 h. These pathways were highlighted by unsupervised principal component analysis (PCA; B), which showed a clear rescue by the G6PD-inhibition treatment on the metabolic reprogramming in iPAH-SMCs. An overview of the main pathways affected by the various treatments is provided in the heat map in C (blue to red = low to high levels of metabolites in that pathway across all replicates). *P < 0.05 and ***P < 0.005.