High glucose- induced endothelial dysregulation has been recognized as an initiation of vascular complications in Type 2 diabetes mellitus (T2DM). Anagliptin is a novel licensed dipeptidyl peptidase-4 (DPP-4) inhibitor for the treatment of T2DM. The effects of anagliptin in high glucose- induced endothelial dysfunction are less reported. In the current study, we found that treatment with anagliptin prevented high glucose- induced reduction of cell viability and increase in LDH release in human umbilical vein endothelial cells (HUVECs). Our results indicate that anagliptin- reduced high glucose- induced increase in mitochondrial ROS and NOX-4 expression. Additionally, anagliptin treatment inhibited high glucose- induced expressions of TXNIP in HUVECs. Importantly, anagliptin treatment downregulated high glucose- induced NLRP3 inflammasome activation, as evidenced by reducing the expressions of NLRP3, ASC, and cleaved caspase-1 (P10). Also, ELISA results demonstrate that anagliptin treatment significantly abolished high glucose- induced maturation of IL-1 beta and IL-18. Mechanistically, we found that anagliptin treatment restored high glucose- induced reduction of SIRT1 expression. Silencing of SIRT1 by transfection with SIRT1 siRNA abolished the inhibitory effects of anagliptin in NLRP3 inflammasome activation. These results display that anagliptin may confer protection against high glucose- induced endothelial injury via SIRT1-dependent inhibition of NLRP3 infammasome activation.
[1]Jilin Univ, China Japan Union Hosp, Dept Cardiovasc Med, 126 Xiantai St, Changchun 130033, Jilin, Peoples R China.
[2]Jilin Prov Precis Med Key Lab Cardiovasc Genet Di, Changchun 130033, Jilin, Peoples R China.
[3]Jilin Univ, China Japan Union Hosp, Dept Pharm, Changchun 130033, Jilin, Peoples R China.
[4]Jilin Univ, China Japan Union Hosp, Dept Pathol, Changchun 130033, Jilin, Peoples R China.
[5]Jilin Univ, China Japan Union Hosp, Dept Anesthesiol, 126 Xiantai St, Changchun 130033, Jilin, Peoples R China.
(8.0+极速模式)