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

Highlights: • HG did not induce endothelial cell injury directly, but increased cell viability after 72 h. • HG triggered upregulation of survivin expression as well as key components of autophagy pathway. • Survivin regulated HG-induced vascular endothelial cell dysfunction mediated by autophagy pathway. 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.