Histological comparison of arterial thrombi in mice and men and the influence of Cl-amidine on thrombus formation

Novotny, Julia; Chandraratne, Sue; Weinberger, Tobias; Philippi, Vanessa; Stark, Konstantin; Ehrlich, Andreas; Pircher, Joachim; Konrad, Ildiko; Oberdieck, Paul; Titova, Anna; Hoti, Qendresa; Schubert, Irene; Legate, Kyle R.; Urtz, Nicole; Lorenz, Michael; Pelisek, Jaroslav; Maßberg, Steffen; Brühl, Marie-Luise von; Schulz, Christian

doi:10.1371/journal.pone.0190728

Cited by 60 publications

(51 citation statements)

References 61 publications

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“…Neutrophil extracellular traps (NETs) are DNA-and histone-containing structures released by neutrophils, and were originally shown to fight bacteria [5]. Recently, NETs and their components were identified in atherosclerotic plaques and arterial thrombi of mice and humans [6][7][8][9][10] as well as in thrombi of patients with PAD [11].…”

Section: Introductionmentioning

confidence: 99%

Surrogate Markers of Neutrophil Extracellular Trap Formation are Associated with Ischemic Outcomes and Platelet Activation after Peripheral Angioplasty and Stenting

Demyanets

Stojković

Mauracher

et al. 2020

JCM

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Neutrophil extracellular traps (NETs) are supposed to play a central role in atherothrombosis. We measured circulating citrullinated histone H3 (H3Cit) and cell-free DNA (cfDNA), which serve as surrogate markers of NET formation, in 79 patients with peripheral artery disease (PAD) following infrainguinal angioplasty with stent implantation. Analysis of cfDNA and H3Cit was performed using Quant-iT™ PicoGreen® dsDNA Assay Kit or an ELISA, respectively. Within two years of follow-up, the primary endpoint defined as nonfatal myocardial infarction, stroke or transient ischemic attack, cardiovascular death, and >80% target vessel restenosis occurred in 34 patients (43%). Both H3Cit (HR per 1-SD: 2.72; 95% CI: 1.2–6.3; p = 0.019) and cfDNA (HR per 1-SD: 2.15; 95% CI: 1.1–4.2; p = 0.028) were associated with the primary endpoint in a univariate Cox regression analysis. Multivariate linear regression analyses showed associations between cfDNA and platelet surface expression of P-selectin (p = 0.006) and activated glycoprotein IIb/IIIa (p < 0.001) in response to arachidonic acid (AA) after adjustment for age, sex, clinical risk factors, and inflammatory markers. H3Cit was also associated with P-selectin expression in response to thrombin-receptor activating peptide (p = 0.048) and AA (p = 0.032). Circulating H3Cit and cfDNA predict ischemic outcomes after peripheral angioplasty with stent implantation, and are associated with on-treatment platelet activation in stable PAD.

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Section: Introductionmentioning

confidence: 99%

Surrogate Markers of Neutrophil Extracellular Trap Formation are Associated with Ischemic Outcomes and Platelet Activation after Peripheral Angioplasty and Stenting

Demyanets

Stojković

Mauracher

et al. 2020

JCM

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“…For instance, the composition of 81 human thrombi obtained during percutaneous coronary intervention for myocardial infarction showed substantial numbers of neutrophils in the thrombus material, cellular sources which could potentially form NETs. 72 Furthermore, immunohistological analyses performed on 68 human ischemic stroke thrombi demonstrated the presence of NETs in the thrombus material. All thrombi were positive on immunostaining for both citrullinated histones and NE and showed colocalization of DNA, neutrophils, and histones by immunofluorescence staining.…”

Section: Neutrophil Extracellular Traps In Thrombotic Complications Omentioning

confidence: 99%

Netting Liver Disease: Neutrophil Extracellular Traps in the Initiation and Exacerbation of Liver Pathology

Meijenfeldt

Jenne

2020

Semin Thromb Hemost

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The liver plays a vital role in the immune system. Its unique position in the portal circulation and the architecture of the hepatic sinusoids, in combination with the wide-ranged population of immunocompetent cells, make the liver function as an immune filter. To aid in pathogen clearance, once challenged, the liver initiates the rapid recruitment of a wide variety of inflammatory cells, including neutrophils. These neutrophils, in conjunction with platelets, facilitate the release of neutrophil extracellular traps (NETs), which are web-like structures of decondensed nuclear DNA, histones, and neutrophil proteins. NETs function as both a physical and a chemical barrier, binding and killing pathogens circulating in the blood stream. In addition to their antimicrobial role, NETs also bind platelets, activate coagulation, and exacerbate host inflammatory response. This interplay between inflammation and coagulation drives microvascular occlusion, ischemia, and (sterile) damage in liver disease. Although direct clinical evidence of this interplay is scarce, preliminary studies indicate that NETs contribute to progression of liver disease and (thrombotic) complications. Here, we provide an overview of the pathological mechanisms of NETs in liver disease. In addition, we summarize clinical evidence for NETs in different disease etiologies and complications of liver disease and discuss the possible implications for the use of NETs as a diagnostic marker and a therapeutic target in liver disease.

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“…The thrombosis models in the inferior vena cava and in the carotid artery were performed according to Aghourian et al 28 and Novotny et al, 29 with minor modifications. To induce thrombus formation, a Whatman filter paper (4 3 2 mm) saturated in 10% FeCl 3 was applied to the vessels and removed after 3 minutes.…”

Section: Vena Cava and Carotid Artery Thrombus Formation Monitoring Umentioning

confidence: 99%

Platelet protein S limits venous but not arterial thrombosis propensity by controlling coagulation in the thrombus

Calzavarini

Prince-Eladnani

Saller

et al. 2020

Blood

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Anticoagulant protein S (PS) in platelets (PSplt) resembles plasma PS and is released on platelet activation, but its role in thrombosis has not been elucidated. Here we report that inactivation of PSplt expression using the Platelet factor 4 (Pf4)-Cre transgene (Pros1lox/loxPf4-Cre+) in mice promotes thrombus propensity in the vena cava, where shear rates are low, but not in the carotid artery, where shear rates are high. At a low shear rate, PSplt functions as a cofactor for both activated protein C and tissue factor pathway inhibitor, thereby limiting factor X activation and thrombin generation within the growing thrombus and ensuring that highly activated platelets and fibrin remain localized at the injury site. In the presence of high thrombin concentrations, clots from Pros1lox/loxPf4-Cre− mice contract, but not clots from Pros1lox/loxPf4-Cre+ mice, because of highly dense fibrin networks. Thus, PSplt controls platelet activation as well as coagulation in thrombi in large veins, but not in large arteries.

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Histological comparison of arterial thrombi in mice and men and the influence of Cl-amidine on thrombus formation

Cited by 60 publications

References 61 publications

Surrogate Markers of Neutrophil Extracellular Trap Formation are Associated with Ischemic Outcomes and Platelet Activation after Peripheral Angioplasty and Stenting

Surrogate Markers of Neutrophil Extracellular Trap Formation are Associated with Ischemic Outcomes and Platelet Activation after Peripheral Angioplasty and Stenting

Netting Liver Disease: Neutrophil Extracellular Traps in the Initiation and Exacerbation of Liver Pathology

Platelet protein S limits venous but not arterial thrombosis propensity by controlling coagulation in the thrombus

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