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 (HO) 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 HO 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 HO-induced HUVECs. MiR-4500 negatively regulates ARG2 expression, meanwhile ameliorating HO-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 HO stimulation in HUVECs. OIP5-AS1 depletion shows the protective effects on HO-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.