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The influence of hyperglycemia on neutrophil extracellular trap formation and endothelial glycocalyx damage in a mouse model of type 2 diabetes.
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.
Duke Scholars
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Related Subject Headings
- Neutrophils
- Neutrophil Activation
- Mice, Transgenic
- Mice
- Male
- Hyperglycemia
- Glycocalyx
- Extracellular Traps
- Endothelium, Vascular
- Diabetes Mellitus, Type 2
Citation
![Journal cover image](https://secure.syndetics.com/index.aspx?isbn=/lc.gif&issn=1549-8719&client=dukeuniv)
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Neutrophils
- Neutrophil Activation
- Mice, Transgenic
- Mice
- Male
- Hyperglycemia
- Glycocalyx
- Extracellular Traps
- Endothelium, Vascular
- Diabetes Mellitus, Type 2