Objective: To investigate high-concentration uric acid-induced endothelial dysfunction mediated by miR-155.
Methods: Human umbilical vein endothelial cells (HUVECs) were incubated with 600 µmol/L uric acid for 24 and 48 h, and eNOS expression and NO content in the cell culture were measured. The target genes of miR-155 were predicted using on-line analysis software and validated by dual-luciferase system. Real-time PCR was used to detect the expression of miR-155 in endothelial cells incubated with high-concentration uric acid. The effect of miR-155 on endothelial dysfunction was assessed by transfection of its inhibitor into HUVECs.
Results: The expression of eNOS and NO secretion decreased obviously in HUVECs incubated with 600 µmol/L uric acid. MicroRNA on-line analysis software and dual luciferase reporter experiments suggested that the level of eNOS translation was directly regulated by miR-155. The expression of miR-155 in endothelial cells was upregulated after stimulation with high-concentration uric acid, and was inhibited by transfection of miR-155 inhibitor. Expression of eNOS and secretion of NO were elevated in endothelial cells transfected with miR-155 inhibitor after incubation with high-concentration uric acid.
Conclusion: High-concentration uric acid can down-regulate eNOS expression via miR-155 to induce endothelial dysfunction.