NETosis in Long-Term Type 1 Diabetes Mellitus and Its Link to Coronary Artery Disease
BackgroundNeutrophil 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...
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.799539/full |
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| author | Sverre Grøver Aukrust Kristine Bech Holte Trine B. Opstad Trine B. Opstad Ingebjørg Seljeflot Ingebjørg Seljeflot Tore Julsrud Berg Tore Julsrud Berg Ragnhild Helseth |
| author_facet | Sverre Grøver Aukrust Kristine Bech Holte Trine B. Opstad Trine B. Opstad Ingebjørg Seljeflot Ingebjørg Seljeflot Tore Julsrud Berg Tore Julsrud Berg Ragnhild Helseth |
| author_sort | Sverre Grøver Aukrust |
| collection | DOAJ |
| description | BackgroundNeutrophil 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.Material and Methods102 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.ResultsCirculating MPO-DNA levels were significantly lower in patients with T1DM than in controls (0.17 vs 0.29 OD, p<0.001), while dsDNA, H3Cit, PAD4 and gene expression of PAD4 did not differ with respect to the presence of T1DM. There were no significant associations between NETs markers and HbA1c in the T1DM group. None of the NETs markers differed according to the presence of CAD in patients with T1DM. While all circulating NETs markers correlated significantly with circulating neutrophils in the control group (r=0.292-393, p<0.014), only H3Cit and PAD4 correlated with neutrophils in the T1DM group (r= 0.330-0.449, p ≤ 0.001).ConclusionsIn this cross-sectional study of patients with long-term T1DM and age-matched controls, circulating NETs levels were not consistently associated with the presence of T1DM or glycemic status, and did not differ according to the presence of CAD in patients with T1DM. Our results entail the possibility of altered neutrophil function and reduced NETosis in T1DM. This warrants further investigation. |
| first_indexed | 2024-12-20T14:01:01Z |
| format | Article |
| id | doaj.art-f29dd0608a3a410eb61af6d1c4809ec7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T14:01:01Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f29dd0608a3a410eb61af6d1c4809ec72022-12-21T19:38:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011210.3389/fimmu.2021.799539799539NETosis in Long-Term Type 1 Diabetes Mellitus and Its Link to Coronary Artery DiseaseSverre Grøver Aukrust0Kristine Bech Holte1Trine B. Opstad2Trine B. Opstad3Ingebjørg Seljeflot4Ingebjørg Seljeflot5Tore Julsrud Berg6Tore Julsrud Berg7Ragnhild Helseth8Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, NorwayDepartment of Endocrinology, Oslo University Hospital Aker, Oslo, NorwayCenter for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, NorwayFaculty of Medicine, University of Oslo, Oslo, NorwayCenter for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, NorwayFaculty of Medicine, University of Oslo, Oslo, NorwayDepartment of Endocrinology, Oslo University Hospital Aker, Oslo, NorwayFaculty of Medicine, University of Oslo, Oslo, NorwayCenter for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, NorwayBackgroundNeutrophil 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.Material and Methods102 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.ResultsCirculating MPO-DNA levels were significantly lower in patients with T1DM than in controls (0.17 vs 0.29 OD, p<0.001), while dsDNA, H3Cit, PAD4 and gene expression of PAD4 did not differ with respect to the presence of T1DM. There were no significant associations between NETs markers and HbA1c in the T1DM group. None of the NETs markers differed according to the presence of CAD in patients with T1DM. While all circulating NETs markers correlated significantly with circulating neutrophils in the control group (r=0.292-393, p<0.014), only H3Cit and PAD4 correlated with neutrophils in the T1DM group (r= 0.330-0.449, p ≤ 0.001).ConclusionsIn this cross-sectional study of patients with long-term T1DM and age-matched controls, circulating NETs levels were not consistently associated with the presence of T1DM or glycemic status, and did not differ according to the presence of CAD in patients with T1DM. Our results entail the possibility of altered neutrophil function and reduced NETosis in T1DM. This warrants further investigation.https://www.frontiersin.org/articles/10.3389/fimmu.2021.799539/fullneutrophil extracellular trapsglucoseneutrophilsNETscoronary artery diseasetype 1 diabetes mellitus |
| spellingShingle | Sverre Grøver Aukrust Kristine Bech Holte Trine B. Opstad Trine B. Opstad Ingebjørg Seljeflot Ingebjørg Seljeflot Tore Julsrud Berg Tore Julsrud Berg Ragnhild Helseth NETosis in Long-Term Type 1 Diabetes Mellitus and Its Link to Coronary Artery Disease Frontiers in Immunology neutrophil extracellular traps glucose neutrophils NETs coronary artery disease type 1 diabetes mellitus |
| title | NETosis in Long-Term Type 1 Diabetes Mellitus and Its Link to Coronary Artery Disease |
| title_full | NETosis in Long-Term Type 1 Diabetes Mellitus and Its Link to Coronary Artery Disease |
| title_fullStr | NETosis in Long-Term Type 1 Diabetes Mellitus and Its Link to Coronary Artery Disease |
| title_full_unstemmed | NETosis in Long-Term Type 1 Diabetes Mellitus and Its Link to Coronary Artery Disease |
| title_short | NETosis in Long-Term Type 1 Diabetes Mellitus and Its Link to Coronary Artery Disease |
| title_sort | netosis in long term type 1 diabetes mellitus and its link to coronary artery disease |
| topic | neutrophil extracellular traps glucose neutrophils NETs coronary artery disease type 1 diabetes mellitus |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.799539/full |
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