ALDR Enhanced Endothelial Injury in Hyperuricemia Screened using SILAC

Background: The exact etiology of hyperuricemia-induced endothelial injury remains ill-defined. To elucidate the mechanism that leads to endothelial injury in hyperuricemia, we investigated proteins expressed in human umbilical vein endothelial cells (HUVECs) cultured with high concentrations of uric acid (HUA) in vitro. Methods: We used stable isotope labeling with amino acids in cell culture (SILAC) combined with LC-MS/MS analysis to compare proteins expressed in HUVECs cultured in media with or without HUA. The results were confirmed by Western blotting. Reactive oxygen species (ROS) were detected using a confocal microscope. Results: Thirty-nine proteins with various cellular functions were differentially expressed. Among them, aldose reductase (ALDR) protein expression was enhanced significantly, indicating increased aldehyde reductase and oxidoreductase activities. ROS levels decreased when ALDR protein activity was inhibited by siALDR. Conclusions: ALDR protein may play an important role in endothelial injury induced by hyperuricemia, and activity of the ALDR protein is associated with oxidative stress