Endothelial cells from umbilical cord of women affected by gestational diabetes: A suitable in vitro model to study mechanisms of early vascular senescence in diabetes

Human umbilical cord endothelial cells (HUVECs) obtained from women affected by gestational diabetes (GD- HUVECs) display durable pro- atherogenic modifications and might be considered a valid in vitro model for studying chronic hyperglycemia effects on early endothelial senescence. Here, we demonstrated that GD- compared to C- HUVECs (controls) exhibited oxidative stress, altered both mitochondrial membrane potential and antioxidant response, significant increase of senescent cells characterized by a reduced NAD- dependent deacetylase sirtuin- 1 (SIRT1) activity together with an increase in cyclin- dependent kinase inhibitor- 2A (P16), cyclin- dependent kinase inhibitor- 1 (P21), and tumor protein p53 (P53) acetylation. This was associated with the p300 activation, and its silencing significantly reduced the GD- HUVECs increased protein levels of P300 and Ac- P53 thus indicating a per-sistent endothelial senescence via SIRT1/P300/P53/P21 pathway. Overall, our data suggest that GD- HUVECs can represent an “endothelial hyperglycemic memory”