Anagliptin ameliorates high glucose- induced endothelial dysfunction via suppression of NLRP3 inflammasome activation mediated by SIRT1. (March 2019)

• Record Type: Journal Article
• Authors: Jiang, Tiechao; Jiang, Dongli; Zhang, Lirong; Ding, Mei; Zhou, Hui
• Is Part Of: Molecular immunology. Volume 107(2019:Mar.)
• Page Start: 54
• Page End: 60
• Publication Date: 2019-03
• Subjects: Type 2 diabetes mellitus -- Anagliptin -- NLRP3 infammasome -- SIRT1 -- Endothelial dysfunciton; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2019.01.006
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: Anagliptin attenuates high glucose- induced cell death, mitochondrial ROS, and NOX-4. Anagliptin attenuates high glucose- induced expression of TXNIP. Anagliptin inhibits NLRP3 inflammasome activation and IL-1β/IL-18 maturation. The effects of Anagliptin on NLRP3 inflammasome activation are mediated by SIRT1. Abstract: 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-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 that anagliptin may confer protection against high glucose- induced endothelial injury via SIRT1-dependent inhibition of NLRP3 infammasome activation.