High Glucose-induced Endothelial Cells Injury Research Articles

Acacetin Protects Against High Glucose-Induced Endothelial Cells Injury by Preserving Mitochondrial Function via Activating Sirt1/Sirt3/AMPK Signals.

The strategy of decreasing atherosclerotic cardiovascular disorder is imperative for reducing premature death and improving quality of life in patients with diabetes mellitus. The aim of this study was to investigate whether the natural flavone acacetin could protect against endothelial injury induced by high glucose and attenuate diabetes-accelerated atherosclerosis in streptozotocin-(STZ) induced diabetic ApoE−/− mice model. It was found that in human umbilical vein endothelial cells (HUVECs) cultured with normal 5.5 mM or high 33 mM glucose, acacetin (0.3–3 μM) exerted strong cytoprotective effects by reversing high glucose-induced viability reduction and reducing apoptosis and excess production of intracellular reactive oxygen species (ROS) and malondialdehyde in a concentration-dependent manner. Acacetin countered high glucose-induced depolarization of mitochondrial membrane potential and reduction of ATP product and mitoBcl-2/mitoBax ratio. Silencing Sirt3 abolished the beneficial effects of acacetin. Further analysis revealed that these effects of acacetin rely on Sirt1 activation by increasing NAD+ followed by increasing Sirt3, pAMPK and PGC-1α. In STZ-diabetic mice, acacetin significantly upregulated the decreased signaling molecules (i.e. SOD, Bcl-2, PGC-1α, pAMPK, Sirt3 and Sirt1) in aorta tissue and attenuated atherosclerosis. These results indicate that vascular endothelial protection of acacetin by activating Sirt1/Sirt3/AMPK signals is likely involved in alleviating diabetes-accelerated atherosclerosis by preserving mitochondrial function, which suggests that acacetin may be a drug candidate for treating cardiovascular disorder in patients with diabetes.

MicroRNA-329-3p alleviates high glucose-induced endothelial cell injury via inhibition of the TLR4/TRAF6/NF-κB signaling pathway.

The aim of the current study was to determine the expression of microRNA (miRNA/miR)-329-3p in patients with type 2 diabetes mellitus (T2DM) and to investigate the effect of miR-329-3p on vascular endothelial cell function under high-glucose conditions. A total of 33 healthy individuals and 31 patients with T2DM were enrolled in the present study. Peripheral blood was collected from all participants. Human umbilical vein endothelial cells (HUVECs) were transfected with a miR-329-3p mimic or miR-329-3p inhibitor. Following treatment with 25 mmol/l glucose, a Cell Counting Kit-8 assay and flow cytometry analysis were used to assess cell viability and apoptosis levels, respectively. A dual luciferase reporter assay, western blot analysis and reverse transcription-quantitative PCR were used to assess molecular mechanism of miR-329-3p in HUVECs. The results revealed that plasma miR-329-3p expression was decreased patients with T2DM compared with healthy controls, and in HUVECs treated with high glucose concentrations. In addition, miR-329-3p reduced high glucose-induced damage to HUVEC cells. miR-329-3p directly bound to toll like receptor (TLR)-4 and regulated its expression at the transcriptional and post-transcriptional levels. miR-329-3p was also demonstrated to be involved in the regulation of the TLR4/tumor necrosis factor receptor associated factor 6 (TRAF6)/nuclear factor (NF)-κB signaling pathway and the nuclear translocation of NF-κB under a high glucose environment. In conclusion, the results indicated that miR-329-3p may protect endothelial cells from high glucose-induced apoptosis via inhibition of the TLR4/TRAF6/NF-κB signaling pathway. The present study also demonstrated that miR-329-3p expression in the plasma of patients with T2DM was reduced, suggesting that upregulation of miR-329-3p may alleviate high glucose-induced endothelial cell injury via inhibition of the TLR4/TRAF6/NF-κB signaling pathway.