The lncRNA OIP5-AS1/miR-4500 axis targeting ARG2 modulates oxidative stress-induced premature senescence in endothelial cells: implications for vascular aging

BACKGROUND: Endothelial senescence due to increased age or oxidative stress can cause endothelial dysfunction, which is strongly associated with the pathogenesis of cardiovascular diseases (CVDs). RESEARCH DESIGN AND METHODS: Hydrogen peroxide (H₂O₂) was used to induced human umbilical vein endothelial cells (HUVECs) senescence model. Cell senescence and cell proliferation were assessed by SA-β-gal staining and PCNA staining. Nitric oxide (NO) and reactive oxygen species (ROS) levels were detected by DAF-2 DA and DCFH-DA. Inflammatory indicators were quantified by qPCR. Meanwhile, western blot was used to examine the ARG2 protein. Finally, an aging mice model induced by H₂O₂ was established to confirm the role of OIP5-AS1/miR-4500/ARG2 in endothelial dysfunction in vivo. RESULTS: ARG2 was upregulated and miR-4500 was reduced in H₂O₂-induced HUVECs. MiR-4500 negatively regulates ARG2 expression, meanwhile ameliorating H₂O₂-induced ECs senescence and dysfunction. Targeted interactions among OIP5-AS1, miR-4500, and ARG2 were confirmed by dual-luciferase reporter assays. OIP5-AS1 as miR4500 sponge negatively mediates miR-4500 expression, and is upregulated upon H₂O₂ stimulation in HUVECs. OIP5-AS1 depletion shows the protective effects on H₂O₂-induced ECs senescence, dysfunction, and SASP. In vivo, a higher expression of OIP5-AS1 and ARG2 in the aortas of aged mice. CONCLUSIONS: We disclosed a regulatory mechanism for OIP5-AS1/miR-4500/ARG2 in the regulation of oxidative stress-related ECs senescence and vascular aging.