The influence of hyperglycemia on neutrophil extracellular trap formation and endothelial glycocalyx damage in a mouse model of type 2 diabetes. (22nd March 2020)

• Record Type: Journal Article
• Authors: Hirota, Tatsuhiko; Levy, Jerrold H.; Iba, Toshiaki
• Is Part Of: Microcirculation. Volume 27:Number 5(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-03-22
• Subjects: diabetes mellitus -- hyperglycemia -- neutrophil extracellular traps -- vascular injuries glycocalyx; Biological transport -- Periodicals; Microcirculation -- Physiology -- Periodicals; 612.135
• DOI: 10.1111/micc.12617
• Languages: English
• ISSNs: 1073-9688

Abstract

Abstract: 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.