Apelin‐13 Inhibits the Adhesion of Monocytes to Endothelial Cells via the Gfi1/NF‐κB Signaling Pathway

ABSTRACT Oxidized low‐density lipoprotein (ox‐LDL)‐induced endothelial dysregulation and the abnormal interaction between monocytes have been considered key risk factors for atherosclerosis. The study investigated the effects of apelin‐13 on ox‐LDL‐induced endothelial dysfunction in human aortic endothelial cells (HAECs). Cells were stimulated with ox‐LDL (100 mg/L), either alone or in combination with apelin‐13 at concentrations of 3 and 6 µM. Multiple techniques, including real‐time PCR, Western blot analysis, enzyme‐linked immunosorbent assay (ELISA), cell attachment assays, and luciferase activity assays, were employed. Our results showed that ox‐LDL reduced the expression of the G‐protein‐coupled apelin receptor (APJ) in HAECs. However, treatment with apelin‐13 reduced the expression of lectin‐like ox‐LDL receptor 1 (LOX‐1) against ox‐LDL and inhibited the expression of pro‐inflammatory cytokines in HAECs. Real‐time PCR and ELISA assay demonstrated that apelin‐13 also inhibited the expression of cell adhesion molecules intercellular cell adhesion molecule‐1 (ICAM‐1) and E‐selectin. The calcein AM staining method displayed that apelin‐13 mitigated ox‐LDL‐induced attachment of THP‐1 monocytes to HAECs. Furthermore, apelin‐13 prevented the reduction of growth factor independence‐1 (Gfi1) and the activation of NF‐κB in HAECs, as evidenced by the luciferase activity assay. Knockdown of Gfi1 counteracted the inhibitory effects of apelin‐13 on the attachment of THP‐1 monocytes to HAECs, suggesting that the protective effects of apelin‐13 in endothelial dysfunction are mediated by the Gfi1/ NF‐κB signaling pathway. These findings suggest that apelin‐13 may have therapeutic potential in preventing atherosclerosis by improving endothelial function and reducing inflammation.