Objective:To investigate the effect of miR-22-3p and apoptosis-inducing factor,mitochondrion-associated 1(AIFM1)on mitochondrial homeostasis and apoptosis of pulmonary artery smooth muscle cells(PASMCs)under hypoxic conditions by establishing an in vitro model of pulmonary hypertension(PAH).Methods:PASMCs were cultured under hypoxic conditions to establish an in vitro model of PAH,and the expression levels of AIFM1 and miR-22-3p were upregulated or downregulated.Reverse transcription quantita-tive polymerase chain reaction(RT-qPCR)and Western blotting were used to measure the expression levels of AIFM1,miR-22-3p,and cleaved cysteine-aspartic protease-3(Cleaved Caspase-3).cell counting kit-8(CCK-8)assay was used to measure the prolifera-tive activity of cells,and flow cytometry was used to measure cell apoptosis.Mitochondrial superoxide indicator(mitoSOX)and adenos-ine triphosphate(ATP)assay kits were used to observe mitochondrial function and dynamics,and Mito-Tracker Red CMXRos(Mito-Tracker)was used to measure the change in mitochondrial circum-ference.Dual-luciferase reporter assay was used to validate the interaction between AIFM1 and miR-22-3p.Results:Hypoxia increased the content of mitochondrial ROS,reduced the level of ATP,promoted mitochondrial fission,and reduced cell apoptosis in PASMCs.AIFM1 overexpression improved mitochondrial homeo-stasis and increased cell apoptosis,while miR-22-3p negatively regulated AIFM1 and reversed the effect of AIFM1 overexpression.Conclusion:This study shows that miR-22-3p enhances mitochon-drial homeostasis,proliferation,and apoptosis in hypoxia-induced PASMCs by targeting AIFM1,which provides a potential theoretical basis for the prevention and treatment of PAH.