Autophagy and Apoptosis in the Response of Human Vascular Endothelial Cells to Oxidized Low-Density Lipoprotein.

Abstract

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.

• Authors: Yanlin Zhang, Ying Xie, Shoujiang You, Qiao Han, Yongjun Cao, Xia Zhang, Guodong Xiao, Rui Chen, Chunfeng Liu
• Journal: Cardiology (Cardiology) Vol. 132 Issue 1 Pg. 27-33 ( 2015) ISSN: 1421-9751 [Electronic] Switzerland
• PMID: 26021729 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipoproteins, LDL
• oxidized low density lipoprotein

Topics

• Apoptosis (physiology)
• Autophagy (physiology)
• Cells, Cultured
• Human Umbilical Vein Endothelial Cells (metabolism)
• Humans
• Lipoproteins, LDL (metabolism)
• Up-Regulation