Abstrakt

Advanced oxidation protein products induce the apoptosis of vascular endothelial cells via activating Nrf2 pathway in atherosclerosis

Dao-Ri-Na Bao, Yu-Qin Jia, Yan-Mei Liu, Li-Feng Zhang, Peng-Fei Wu, Xiao-Xue Wang, Heng-Bin Li, Xing-Yong Wang

Objective: To explore the influence of Advanced Oxidation Protein Products (AOPPs) on vascular endothelial cells proliferation and apoptosis and the role of Nrf2 pathway in the process.

Methods: Different concentrations of AOPPs were used to treat vascular endothelial cells (HUVEC) for 12, 24 and 48 h. Vascular endothelial cells were treated with high, middle and low concentrations of AOPPs for 24 h and flow cytometry was used to determine the changes of cell cycle, apoptosis and reactive oxygen species. Western blotting was used to determine the protein expression of Caspase 3, Caspase 8, Caspase 9, Nrf2 and its downstream gene HO-1.

Results: The vascular endothelial cell viability decreased gradually with the increase of AOPPs concentrations from 0 ug/ml to 50 ug/ml, and then further decreased with the increase of concentrations from 50 ug/ml to 200 ug/ml, and the time had no influence on cell viability. Therefore, concentrations of 2, 50 and 200 ug/mL and time of 24 h were used for the further study. Vascular endothelial cells mainly focused at G1 stage at high concentration of AOPPs. The number of apoptotic cells, as well as reactive oxygen and expressions of Caspase 3, Caspase 8, Caspase 9, Nrf2 and HO-1, increased with the increase of AOPPs concentrations.

Conclusion: In atherosclerosis, AOPPs could induce the apoptosis of vascular endothelial cells and inhibit the proliferation by activating Nrf2 pathway.