Survivin regulated by autophagy mediates hyperglycemia-induced vascular endothelial cell dysfunction

Exp Cell Res. 2018 Mar 15;364(2):152-159. doi: 10.1016/j.yexcr.2018.01.037. Epub 2018 Jan 31.


Diabetic vascular complications are often defined by vascular endothelial lesions. However, as a plastic cell type, whether endothelial cells could transit from quiescence to hyper-active status and hamper vascular stability upon hyperglycemia stimulation and whether this process is involved in diabetic vascular complications remain obscure. Survivin has been identified as an anti-apoptotic protein in tumor or epithelial cells by either promoting proliferation or inhibiting apoptosis. Therefore, this study aims at investigating the effects of hyperglycemia on endothelial cell status and the potential involvement of survivin. We found that high glucose (25 mM) did not cause endothelial injuries, instead, it evidently promotes endothelial proliferation and tube formation capacity indicating endothelial cell dysfunction upon hyperglycemia characterized by its preference to hyper-active status. Concomitantly, an upregulation of survivin was detected accompanied by the key component elevations of autophagy pathway including LC3, Beclin1, and p62. YM155, a specific inhibitor of survivin, could abrogate hyperglycemia-induced endothelial hyper-activation. Application of the autophagy inhibitor (3MA) and agonist (rapamycin) supported that survivin could be as a downstream effect or of autophagy. Thus, our results suggested that survivin/autophagy axis a potential therapeutic target in treatment of diabetic vascular complications.

Keywords: Autophagy; Hyperglycemia; Survivin; Vascular endothelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy*
  • Cell Proliferation
  • Cell Survival
  • Cells, Cultured
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology
  • Humans
  • Hyperglycemia / metabolism*
  • Hyperglycemia / pathology
  • Survivin / metabolism*


  • BIRC5 protein, human
  • Survivin