circMFN2 reguleert IGF2BP3-PDK4 bij pulmonale hypertensie

BACKGROUND:Circular RNAs have emerged as key regulators of vascular remodeling and promising therapeutic targets, yet their specific contributions to pulmonary hypertension (PH) remain largely unknown.METHODS:We identified a PH-related circular RNA, circMFN2, generated from the MFN2 (mitofusin-2) locus, which was significantly downregulated in the peripheral blood of patients with PH and in pulmonary arteries of Sugen/hypoxia–induced PH mice. Functional studies were performed in human pulmonary artery smooth muscle cells under hypoxic conditions and in Sugen/hypoxia mice treated intranasally with R8-circMFN2 (R8-peptide–modified liposomal circMFN2). Transcriptomic profiling, RNA-protein interaction assays, and mitochondrial function analyses were used to define the downstream mechanisms.RESULTS:circMFN2 overexpression significantly attenuated hypoxia-induced human pulmonary artery smooth muscle cell proliferation, migration, and mitochondrial dysfunction. RNA sequencing after circMFN2