In pulmonary arterial hypertension, hypoxic mitochondrial reactive oxygen species (mtROS) inhibit the hydroxylation of hypoxia inducible factor-1α (HIF-1α), activating the HIF-1α/PDK1-2/p-PDH-E1α axis (hypoxia inducible factor-1α/Pyruvate dehydrogenase kinase isozyme1-2/phosphorylated pyruvate dehydrogenase E1 alpha subunit, HIF-1α/PDK1-2/p-PDH-E1α) to enhance glycolysis, lactate accumulation, and histone lactylation (H3K18/H4K5la), driving the proliferation of smooth muscle cells in pulmonary artery walls [40]. The gene discussed is HIF1A; the disease is pulmonary arterial hypertension.