scholarly journals Assessment of Neutrophil Extracellular Traps in Coronary Thrombus of a Case Series of Patients With COVID-19 and Myocardial Infarction

2020 ◽  
Author(s):  
Ana Blasco ◽  
María-José Coronado ◽  
Fernando Hernández-Terciado ◽  
Paloma Martín ◽  
Ana Royuela ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Case Series ◽  
Neutrophil Extracellular Traps ◽  
Extracellular Traps ◽  
Coronary Thrombus

scholarly journals Neutrophil extracellular traps induce MCP-1 release from endothelial cells at the plaque rupture site in acute myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Ondracek ◽  
T.M Hofbauer ◽  
A Mangold ◽  
T Scherz ◽  
V Seidl ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Endothelial Cells ◽  
Plaque Rupture ◽  
Ex Vivo ◽  
Coronary Intervention ◽  
Neutrophil Extracellular Traps ◽  
Funding Source ◽  
Extracellular Traps

Abstract Introduction Leukocyte-mediated inflammation is crucial in acute myocardial infarction (AMI). We recently observed that neutrophil extracellular traps (NETs) are increased at the culprit site, promoting activation and differentiation of fibrocytes, cells with mesenchymal and leukocytic properties. Fibrocyte migration is mediated by monocyte chemoattractant protein (MCP)-1 and C-C chemokine receptor type 2 (CCR2). We investigated the interplay between NETs, fibrocyte function, and MCP-1 in AMI. Methods Culprit site and femoral blood of AMI patients was drawn during percutaneous coronary intervention. We characterized CCR2 expression of fibrocytes by flow cytometry. MCP-1 and the NET marker citrullinated histone H3 (citH3) were measured by ELISA. Fibrocytes were treated in vitro with MCP-1. Human coronary arterial endothelial cells (hCAECs) were stimulated with isolated NETs, and MCP-1 was measured by ELISA and qPCR. The influence of MCP-1 on NET formation in vitro was assessed using isolated neutrophils. Results We have included 50 consecutive AMI patients into the study. NETs and concentrations of MCP-1 were increased at the CLS. NET stimulation of hCAECs induced MCP-1 on mRNA and protein level. Increasing MCP-1 gradient was associated with fibrocyte accumulation at the site of occlusion. In the presence of higher MCP-1 these fibrocytes expressed proportionally less CCR2 than peripheral fibrocytes. In vitro, MCP-1 dose-dependently decreased fibrocyte CCR2 and reduced ex vivo NET release of healthy donor neutrophils. Conclusions NETs induce endothelial MCP-1 release, presumably promoting a chemotactic gradient for leukocyte and fibrocyte migration. MCP-1 mediated inhibition of NET formation could point to a negative feedback loop. These data will shed light on vascular healing. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Austrian Science Fund

scholarly journals Loss of Sirt3 accelerates arterial thrombosis by increasing formation of neutrophil extracellular traps and plasma tissue factor activity

2018 ◽  
Vol 114 (8) ◽  
pp. 1178-1188 ◽  
Author(s):  
Daniel S Gaul ◽  
Julien Weber ◽  
Lambertus J van Tits ◽  
Susanna Sluka ◽  
Lisa Pasterk ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Bone Marrow ◽  
Arterial Thrombosis ◽  
Ex Vivo ◽  
Neutrophil Extracellular Traps ◽  
Wild Type ◽  
Rotational Thromboelastometry ◽  
Extracellular Traps

AbstractAimsSirtuin 3 (Sirt3) is a mitochondrial, nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that reduces oxidative stress by activation of superoxide dismutase 2 (SOD2). Oxidative stress enhances arterial thrombosis. This study investigated the effects of genetic Sirt3 deletion on arterial thrombosis in mice in an inflammatory setting and assessed the clinical relevance of these findings in patients with ST-elevation myocardial infarction (STEMI).Methods and resultsUsing a laser-induced carotid thrombosis model with lipopolysaccharide (LPS) challenge, in vivo time to thrombotic occlusion in Sirt3−/− mice (n = 6) was reduced by half compared to Sirt3+/+ wild-type (n = 8, P < 0.01) controls. Ex vivo analyses of whole blood using rotational thromboelastometry revealed accelerated clot formation and increased clot stability in Sirt3−/− compared to wild-type blood. rotational thromboelastometry of cell-depleted plasma showed accelerated clotting initiation in Sirt3−/− mice, whereas overall clot formation and firmness remained unaffected. Ex vivo LPS-induced neutrophil extracellular trap formation was increased in Sirt3−/− bone marrow-derived neutrophils. Plasma tissue factor (TF) levels and activity were elevated in Sirt3−/− mice, whereas plasma levels of other coagulation factors and TF expression in arterial walls remained unchanged. SOD2 expression in bone marrow -derived Sirt3−/− neutrophils was reduced. In STEMI patients, transcriptional levels of Sirt3 and its target SOD2 were lower in CD14+ leukocytes compared with healthy donors (n = 10 each, P < 0.01).ConclusionsSirt3 loss-of-function enhances experimental thrombosis in vivo via an increase of neutrophil extracellular traps and elevation of TF suggesting thrombo-protective effects of endogenous Sirt3. Acute coronary thrombosis in STEMI patients is associated with lower expression levels of SIRT3 and SOD2 in CD14+ leukocytes. Therefore, enhancing SIRT3 activity by pan-sirtuin activating NAD+-boosters may provide a novel therapeutic target to prevent or treat thrombotic arterial occlusion in myocardial infarction or stroke.

scholarly journals Neutrophil Extracellular Traps in Arterial and Venous Thrombosis

2019 ◽  
Vol 45 (01) ◽  
pp. 086-093 ◽  
Author(s):  
Elodie Laridan ◽  
Kimberly Martinod ◽  
Simon De Meyer
Keyword(s):  
Myocardial Infarction ◽  
Thrombus Formation ◽  
Neutrophil Extracellular Traps ◽  
Major Health ◽  
Vein Thrombosis ◽  
Extracellular Traps ◽  
Thrombotic Complications ◽  
Decondensed Chromatin ◽  
Deep Vein ◽  
Novel Therapeutic

AbstractThrombotic complications are still a major health risk worldwide. Our view on the pathophysiology of thrombosis has significantly changed since the discovery of neutrophil extracellular traps (NETs) and their prothrombotic characteristics. Generated by neutrophils that release their decondensed chromatin as a network of extracellular fibers, NETs promote thrombus formation by serving as a scaffold that activates platelets and coagulation. The thrombogenic involvement of NETs has been described in various settings of thrombosis, including stroke, myocardial infarction, and deep vein thrombosis. The aim of this review is to summarize existing evidence showing the presence of NETs in human thrombus material. Following an introduction on NETs and their role in thrombus formation, the authors address studies showing the presence of NETs in arterial or venous thrombi. In addition, they focus on potential novel therapeutic opportunities to resolve or prevent thrombosis by targeting NETs.

scholarly journals Neutrophil extracellular traps and monocyte subsets at the culprit lesion site of myocardial infarction patients

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Andreas Mangold ◽  
Thomas M. Hofbauer ◽  
Anna S. Ondracek ◽  
Tyler Artner ◽  
Thomas Scherz ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Infarct Size ◽  
Neutrophil Extracellular Traps ◽  
Lesion Site ◽  
Monocyte Subsets ◽  
Culprit Lesion ◽  
Extracellular Traps ◽  
Classical Monocytes ◽  
Intermediate Monocytes ◽  
Cx3cr1 Expression

Abstract Neutrophils release their chromatin into the extracellular space upon activation. These web-like structures are called neutrophil extracellular traps (NETs) and have potent prothrombotic and proinflammatory properties. In ST-elevation myocardial infarction (STEMI), NETs correlate with increased infarct size. The interplay of neutrophils and monocytes impacts cardiac remodeling. Monocyte subsets are classified as classical, intermediate and non-classical monocytes. In the present study, in vitro stimulation with NETs led to an increase of intermediate monocytes and reduced expression of CX3CR1 in all subsets. Intermediate monocytes have been associated with poor outcome, while non-classical CX3CR1-positive monocytes could have reparative function after STEMI. We characterized monocyte subsets and NET markers at the culprit lesion site of STEMI patients (n = 91). NET surrogate markers were increased and correlated with larger infarct size and with fewer non-classical monocytes. Intermediate and especially non-classical monocytes were increased at the culprit site compared to the femoral site. Low CX3CR1 expression of monocytes correlated with high NET markers and increased infarct size. In this translational system, causality cannot be proven. However, our data suggest that NETs interfere with monocytic differentiation and receptor expression, presumably promoting a subset shift at the culprit lesion site. Reduced monocyte CX3CR1 expression may compromise myocardial salvage.

scholarly journals The Time Course of Markers of Neutrophil Extracellular Traps in Patients Undergoing Revascularisation for Acute Myocardial Infarction or Stable Angina Pectoris

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Ragnhild Helseth ◽  
Svein Solheim ◽  
Harald Arnesen ◽  
Ingebjørg Seljeflot ◽  
Trine Baur Opstad
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Angina Pectoris ◽  
Infarct Size ◽  
Stable Angina ◽  
Troponin T ◽  
Neutrophil Extracellular Traps ◽  
Stable Angina Pectoris ◽  
Extracellular Traps ◽  
Creatine Kinase Mb

Background and Aims. Neutrophil extracellular traps (NETs) have been identified in acute myocardial infarction. We assessed the time profile and association with infarct size for NETs markers in ST-elevation myocardial infarction (STEMI) and stable angina pectoris (AP). Methods. In 20 patients with STEMI and 10 with AP undergoing percutaneous coronary intervention (PCI), blood samples were collected before PCI (only AP group) and after 3 and 12 hours, days 1, 3, 5, 7, and 14 for measurement of NETs markers. Results. Double-stranded deoxyribonucleic acid (dsDNA) and nucleosome levels were higher in STEMI than AP until day 3 and 12 hours (p<0.03, all). DsDNA declined after day 5 in both groups (p<0.04, all), while nucleosomes declined until day 3 only in the AP group (p<0.05, all). DsDNA correlated with peak troponin T and creatine kinase MB (CKMB) at day 5 (r=0.48, p=0.03, both) and with MRI-measured infarct size at days 5 and 7 (r=0.61, p=0.01 and r=0.52, p=0.04, resp.), while nucleosomes correlated with infarct size at day 5 (r=0.58, p=0.02). Conclusions. High levels of NETs markers were observed in STEMI shortly after revascularisation and were partly associated with infarct size. The decline thereafter in both groups indicates a role for NETs in both acute and chronic atherothrombosis.

Neutrophils, neutrophil extracellular traps and interleukin-17 associate with the organisation of thrombi in acute myocardial infarction

2013 ◽  
Vol 109 (02) ◽  
pp. 290-297 ◽  
Author(s):  
Xiaofei Li ◽  
Peter Teeling ◽  
Claire Mackaay ◽  
Hanneke Ploegmakers ◽  
Chris van der Loos ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Platelet Aggregation ◽  
Neutrophil Elastase ◽  
Neutrophil Extracellular Traps ◽  
Histone H1 ◽  
Interleukin 17 ◽  
Double Staining ◽  
Extracellular Traps ◽  
Organized Thrombus

SummaryNeutrophils are important cellular sources of interleukin (IL) 17A and –F. Moreover, upon activation neutrophils are able to excrete chromatin embedded with components from their cytoplasmic granules to form ‘neutrophil extracellular traps’ (NETs). Recent studies suggested that NETs contribute to thrombosis by promoting fibrin deposition and platelet aggregation. IL17A may also promote thrombosis by enhancing platelet aggregation. In the present study we investigated the presence of neutrophils, NETs and IL17A and –F in coronary thrombosuction specimens obtained from patients after acute myocardial infarction. Neutrophils and NETs were identified using histochemical (H&E, Feulgen procedure) and immunohistochemical stainings (Histone H1, myeloperoxidase, neutrophil elastase) in 15 fresh, 15 lytic and 15 organised thrombi. The presence and distribution of IL17A and –F was studied using (immuno)histochemical double staining and spectral image analysis, rtPCR and Western blot. High numbers of neutrophils are present (10–30% of the thrombus mass) in fresh and lytic, but not in organized thrombus. NETs were frequently observed in fresh (4/15) and lytic (12/15), but never in organised thrombus specimens. Double staining combining the Feulgen reaction with Histone- H1, MPO or neutrophil elastase confirmed colocalisation with DNA. Cytoplasmatic IL17A/F staining was found in the majority of the neutrophils, extracellularly and in NETs. Western blotting confirmed the presence of IL17A and IL17F in thrombus specimens. In conclusion, a large burden of neutrophils, neutrophil extracellular traps and IL17A and –F are important constituents of fresh and lytic thrombus after acute myocardial infarction. The specific colocalisation of these indicates a role during thrombus stabilisation and growth.

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