This indicates that elevated arginase activity is a critical factor leading to dysregulated arginine metabolism and impaired NO synthesis in PAH patients, and inter-individual differences in arginase activity may influence disease phenotype and therapeutic response (87).Meanwhile, citrate accumulates in M1 macrophages and is cleaved by ATP–citrate lyase to generate acetyl-CoA, driving inflammatory lipid synthesis, NADPH production, and histone acetylation, thereby amplifying the expression of pro-inflammatory cytokines such as IL-1β (88, 89). Here, IL1B is linked to pulmonary arterial hypertension.