Objectives: Oxidized low-density lipoprotein (ox-LDL) may induce autophagy, apoptosis, necrosis or proliferation of cultured endothelial cells depending on the concentration and exposure time. Our previous studies found that ox-LDL exposure for 6 h increases the autophagic level of human umbilical vein endothelial cells (HUVECs) in a concentration-dependent manner. The present study investigates the relationship between autophagy and apoptosis in HUVECs exposed to ox-LDL. Methods: Flow cytometry and Western blot were used to study the apoptotic and autophagic phenomena. The contribution of autophagic and apoptotic mechanisms to ox-LDL-induced upregulation of MAP1-LC3, beclin1 and p53 protein levels were assessed by pretreatment with the autophagic inhibitors 3-MA and Atg5 small interfering (si)RNA, as well as z-vad-fmk, an apoptosis inhibitor. Results: ox-LDL induced the apoptosis of HUVECs in a concentration-dependent way. The increased expression of the autophagic proteins, LC3-II and beclin1, can be reversed by 3-MA and z-vad-fmk pretreatment. 3-MA and Atg5 siRNA increased the ox-LDL-induced increases of the p53 protein level and the annexin V-positive staining, which was decreased by z-vad-fmk. Conclusion: These results suggest that overstimulation of ox-LDL can induce autophagy and apoptosis in HUVECs. Inhibition of apoptosis leads to an inhibition of autophagy induced by ox-LDL. However, inhibition of autophagy leads to an increase in the ox-LDL-induced apoptosis.

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