NETosis in Long-Term Type 1 Diabetes Mellitus and Its Link to Coronary Artery Disease

Neutrophil extracellular traps NETs have been linked to glucose and the pathogenesis of type 1 diabetes mellitus (T1DM). NETs also play a role in vascular inflammation and the development of coronary artery disease (CAD). The role of NETs in CAD progression in patients with long-term T1DM is unclear...

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Published in:Frontiers in immunology 2022-01, Vol.12, p.799539-799539
Main Authors: Aukrust, Sverre Grøver, Holte, Kristine Bech, Opstad, Trine B, Seljeflot, Ingebjørg, Berg, Tore Julsrud, Helseth, Ragnhild
Format: Article
Language:English
Subjects:
Aged
Biomarkers - blood
Citrullination
coronary artery disease
Coronary Artery Disease - blood
Coronary Artery Disease - metabolism
Cross-Sectional Studies
Diabetes Mellitus, Type 1 - blood
Diabetes Mellitus, Type 1 - metabolism
DNA - blood
Extracellular Traps - metabolism
Female
glucose
Histones - blood
Histones - metabolism
Humans
Immunology
Leukocyte Count
Male
Middle Aged
NETs
neutrophil extracellular traps
neutrophils
Neutrophils - metabolism
Peroxidase - blood
Protein-Arginine Deiminase Type 4 - blood
Time Factors
type 1 diabetes mellitus
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Summary:Neutrophil extracellular traps NETs have been linked to glucose and the pathogenesis of type 1 diabetes mellitus (T1DM). NETs also play a role in vascular inflammation and the development of coronary artery disease (CAD). The role of NETs in CAD progression in patients with long-term T1DM is unclear. We aimed to 1) investigate whether levels of circulating NETs markers were elevated in long-term T1DM subjects compared to controls, and 2) explore whether levels of NETs were related to the presence of CAD. 102 patients with > 45 years of T1DM and 75 age-matched controls were enrolled in a cross-sectional study. Median age was 62 years. Computed tomography coronary angiography (CTCA) was performed in 148 subjects without established coronary heart disease. For the current study, CAD was defined as a coronary artery stenosis >50%. Double-stranded deoxyribonucleic acid (dsDNA) was measured by a nucleic acid stain, myeloperoxidase-DNA (MPO-DNA), citrullinated histone 3 (H3Cit) and peptidylarginine deiminase 4 (PAD4) by ELISAs, while gene expression of PAD4 was measured in leukocytes from PAXgene tubes. Circulating MPO-DNA levels were significantly lower in patients with T1DM than in controls (0.17 vs 0.29 OD, p
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.799539