In the present study, we constructed a PAH model in vitro by hypoxia stimulation PAMSCs, and demonstrated that miR-340-5p negatively regulated MFF to alleviate mitochondrial dysfunction and proliferation–apoptosis balance of hypoxia-stimulated PAMSCs by suppressing SIRT1/3 signaling. This evidence concerns the gene SIRT1 and pulmonary arterial hypertension.