This study aims to explore potential mitochondrial oxidative stress-related biomarkers in IPAH via integrated bioinformatics, validate these genes in MCT-induced rat PAH model and examine the functional roles of COX6B1 and HMGCL in mitochondrial oxidative stress in PDGF-induced pulmonary arterial smooth muscle cells (PASMCs). This evidence concerns the gene COX6B1 and idiopathic pulmonary arterial hypertension.