Anagliptin ameliorates high glucose- induced endothelial dysfunction via suppression of NLRP3 inflammasome activation mediated by SIRT1

Publication date: March 2019Source: Molecular Immunology, Volume 107Author(s): Tiechao Jiang, Dongli Jiang, Lirong Zhang, Mei Ding, Hui ZhouAbstractHigh 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-1β 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 ...
Source: Molecular Immunology - Category: Allergy & Immunology Source Type: research