Figure 7.

PC inhibitor attenuated glycolytic shift and metabolic reprogramming in pulmonary hypertension. In the sugen/hypoxic PAH model, phosphorylation of Akt upregulated cellular glucose uptake and glycolysis. This results in decreased oxidative phosphorylation, increased anaplerosis, and a reduction in glycogenesis. Increased anaplerosis and lactic acidosis feed-forward increased cellular proliferation and vascular remodeling in PAH. PC inhibitor treatment balanced cellular glucose influx, glycogen synthesis, and raised pentose phosphate pathway. As a result, glycolytic shift and improved oxidative phosphorylation returned back to control by inhibiting the key anaplerotic enzyme, PC, in PAH. Thus, proliferative pathological changes in PAH were found to be preserved with PC inhibitor treatment. PAH—pulmonary arterial hypertension, iPC–PC inhibitor, GSK3β–Glycogen synthase kinase 3 beta, G6PD–glucose-6 phosphate dehydrogenase, LDHA—lactate dehydrogenase—A, PC–pyruvate carboxylase, PDH—pyruvate dehydrogenase, OAA—oxaloacetate, TCA—tricarboxylic acid cycle, PAH—pulmonary arterial hypertension.