In PAH, a shift of energy metabolism from OXPHOS of glucose to cytoplasmic glycolysis in PASMCs and PAECs has been widely demonstrated in human lung-derived cell cultures and multiple mouse models of PAH, and the prevailing view is that the driving force for this metabolic shift stems from the pathological accumulation of hypoxia-inducible factor 1α (HIF-1α) [99]. This evidence concerns the gene HIF1A and pulmonary arterial hypertension.