LncRNA MIR210HG promotes phenotype switching of pulmonary arterial smooth muscle cells through autophagy-dependent ferroptosis pathway

<bold>Background:</bold> Excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) serves as the underlying pathogenesis of Hypoxic pulmonary hypertension, accompanied by the transition of PASMCs from a contractile phenotype to a synthetic phenotype. This study aims to investigate the molecular mechanism by which MIR210HG regulates the phenotypic switching of PASMCs. <bold>Methods:</bold> Western blot and immunofluorescence staining were employed to assess the protein levels of OPN, α-SMA, PTGS2, TFR1, LC3-Ⅱ, Beclin-1 in rat lung tissue and PASMCs. RT-PCR quantitative was utilized to determine the expression level of LncRNA MIR210HG in PASMCs. LPO, ROS and GSH/GSSG kits were used to evaluate the ferroptosis levels in PAMSCs. The indirect regulatory relationship between STAT3, HIF-2α and MIR210HG was detected by transfection of STAT3, HIF-2α and MIR210HG overexpression plasmid and siRNA. The Chromatin immunoprecipitation and Luciferase assay were used to detect transcription factor patterns. <bold>Results:</bold> The transcription of MIR210HG is regulated by STAT3 and elevated MIR210HG promotes the transition from a contractile phenotype to a synthetic phenotype in PASMCs under hypoxia by promoting the levels of HIF-2α and then activating the autophagy-dependent ferroptosis pathway. <bold>Conclusions:</bold> Our findings suggest a potential mechanism of LncRNA MIR210HG in HPHand offer potential intervention targets. <fig><object-id>erj;64/suppl_68/PA1607/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>