The influence of hyperglycemia on neutrophil extracellular trap formation and endothelial glycocalyx damage in a mouse model of type 2 diabetes.

Journal Article (Journal Article)

OBJECTIVES: Hyperglycemia induces vascular dysfunction that is thought to be initiated by neutrophils. Neutrophil activation produces endothelial injury by pathways that include NETosis, a type of specific cell death. In this study, we investigated the effects of hyperglycemia on neutrophil activation, cell death, NETosis, and endothelial glycocalyx damage using a mouse diabetes model. METHODS: We used db/db mice as a type 2 diabetes model, and C57BL/6 mice were the controls. At 5, 8, and 12 weeks of age, the proportion of CD11b+ granulocytes/monocytes, neutrophil extracellular trap (NET)-forming granulocytes/monocytes, and damaged and nonviable granulocytes/monocytes was analyzed. In addition, serum levels of high mobility group box 1, histone H3, and glycocalyx components that included syndecan-1 and hyaluronan were measured. RESULTS: In diabetic mice, we observed an increased proportion of CD11b+ granulocytes/monocytes. The proportion of NET-forming granulocytes/monocytes increased from the early stages of the experiments. The proportions of damaged and nonviable granulocytes/monocytes increased over time. In the 12-week-old diabetic mice, serum histone H3 levels increased. Circulating levels of syndecan-1 and hyaluronan decreased over time and were lower in diabetic mice. CONCLUSION: Neutrophil activation and cell death induce endothelial glycocalyx damage, and NET formation also participates in the mechanisms of vascular injury in type 2 diabetes.

Full Text

Duke Authors

Cited Authors

  • Hirota, T; Levy, JH; Iba, T

Published Date

  • July 2020

Published In

Volume / Issue

  • 27 / 5

Start / End Page

  • e12617 -

PubMed ID

  • 32125048

Electronic International Standard Serial Number (EISSN)

  • 1549-8719

Digital Object Identifier (DOI)

  • 10.1111/micc.12617

Language

  • eng

Conference Location

  • United States