Pulmonary artery smooth muscle cells with pulmonary arterial hypertension depends metabolism on glycolysis under normoxia and mitochondrial respiration under hypoxia

The metabolic state of pulmonary artery smooth muscle cells (PASMCs) from patients with pulmonary arterial hypertension (PAH) is not well understood. In this study, we examined the balance between glycolysis and mitochondrial respiration in non-PAH-PASMCs and PAH-PASMCs under normoxia and hypoxia. Under both normoxia and hypoxia, the mRNA and protein levels of pyruvate dehydrogenase kinase 1 (PDK1) and pyruvate dehydrogenase (PDH) were increased in PAH-PASMCs compared with non-PAH-PASMCs. The level of lactate dehydrogenase (LDH) mRNA, as well as the intracellular lactate concentration, was also increased in PAH-PASMCs compared with non-PAH-PASMCs under normoxic conditions. However, LDH mRNA and the intracellular lactate concentration was not significantly increased in PAH-PASMCs compared with non-PAH-PASMCs under hypoxic conditions. Cellular oxygen consumption rates (OCR) were significantly lower in PAH-PASMCs than non-PAH-PASMCs under normoxia. Under hypoxia, however, OCR levels were significantly higher in PAH-PASMCs than non-PAH-PASMCs. Extracellular acidification rates were significantly higher in PAH-PASMCs than non-PAH-PASMCs under both normoxic and hypoxic conditions. These data suggest that glycolysis is favored under normoxic conditions, while mitochondrial respiration is preserved under hypoxia specifically in PAH-PASMCs. These metabolic characteristics of PAH-PASMCs may be important for the pathogenic features of PAH, such as the resistance to hypoxia.