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.

scholarly journals Circulating Monocyte Subsets Are Associated With Extent of Myocardial Injury but Not With Type of Myocardial Infarction

2021 ◽  
Vol 8 ◽  
Author(s):  
Noushin Askari ◽  
Christoph Lipps ◽  
Sandra Voss ◽  
Nora Staubach ◽  
Dimitri Grün ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Myocardial Injury ◽  
Stable Coronary Artery Disease ◽  
Inflammatory Cells ◽  
Monocyte Subsets ◽  
Coronary Syndrome ◽  
Monocyte Subpopulations ◽  
Artery Disease ◽  
Classical Monocytes ◽  
Intermediate Monocytes

Inflammation is a hallmark of the period after a myocardial infarction (MI) that is either promoted or resolved by distinct subtypes of circulating inflammatory cells. The three main monocyte subpopulations play different roles inflammation. This study examined whether the type of MI (type 1 or type 2) or the extent of myocardial injury is associated with differences in monocyte subpopulations. For this purpose, peripheral whole blood from patients with a suspected MI was used for flow cytometric measurements of the monocyte subpopulations, and myocardial injury was classified by cardiac troponin levels in serum. In patients with acute coronary syndrome (n = 82, 62.2% male) similar proportions of the monocyte subsets were associated with the two types of MI, whereas total monocyte counts were increased in patients with substantial myocardial injury vs. those with minor injury (p = 0.045). This was accompanied by a higher proportion of intermediate (p = 0.045) and classical monocytes (p = 0.059); no difference was found for non-classical monocytes (p = 0.772). In patients with chronic coronary syndrome (n = 144, 66.5% male), an independent association with myocardial injury was also observed for classical monocytes (p = 0.01) and intermediate monocytes (p = 0.08). In conclusion, changes in monocyte subpopulation counts, particularly for classical and intermediate monocytes, were related to the extent of myocardial injury in acute and stable coronary artery disease but not to the type of MI.

Abstract 12930: Neutrophil Extracellular Traps Correlate With Impaired Myocardial Reperfusion in Patients With St Elevation Myocardial Infarction After Primary Percutaneous Coronary Intervention

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Mie Kurata ◽  
Anouchska S Autar ◽  
Daniëlle Mensink ◽  
Dirk J Duncker ◽  
Hugo t Cate ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Troponin T ◽  
Coronary Intervention ◽  
Neutrophil Extracellular Traps ◽  
Myocardial Reperfusion ◽  
Culprit Lesion ◽  
Extracellular Traps ◽  
Percutaneous Coronary ◽  
St Elevation ◽  
Dna Complex

Introduction: Impaired myocardial reperfusion after successful percutaneous coronary intervention (PCI) is an important determinant of prognosis of patients with ST elevation myocardial infarction (STEMI). Neutrophil extracellular traps (NETs) are toxic DNA-protein complexes, upregulated in pro-thrombotic states and may induce endothelial injury. Aim: We aimed to assess in systemic and culprit coronary plasma, the level of NETs and their relationship with microvascular perfusion after PCI. Methods: Forty-nine STEMI patients treated with thrombectomy and PCI were enrolled. Patients with past history of coronary revascularization were excluded. Systemic blood was drawn at baseline and post PCI, and from the culprit lesion during thrombectomy. NETs and extracellular histone-DNA (E-DNA) were measured by capture ELISA (myeloperoxidase-DNA complex, histone-DNA complex, respectively). Corrected thrombolysis in MI (TIMI) frame count (cTFC) was calculated from coronary angiography. Results: The relation between NETs and cTFC is summarized in the figure. Both NETs and E-DNA were highest in culprit lesion plasma (p<0.05). Baseline and post-PCI levels of NETs were similar (p=0.56). Baseline, aspirate, and post-PCI NETs levels were inversely correlated with cTFC (ρ=-0.43, -0.31, -0.39, respectively, all p<0.05), and baseline NETs was an independent predictor of cTFC (β=-0.40, p=0.04), not age, gender, total ischemia time or troponin T level at admission. All E-DNA levels positively correlated with troponin T at admission (ρ=0.58, 0.47, 0.38, p<0.05, respectively), and were higher post PCI than at baseline (p<0.01), suggesting a reflection of myocardial damage. E-DNA showed no correlation with cTFC. Conclusions: Prior to PCI, baseline NETs level predict impaired reperfusion and may assist in tailored therapy and follow up.

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 Human T Cell Leukemia Virus Type 1 Infection of the Three Monocyte Subsets Contributes to Viral Burden in Humans

2015 ◽  
Vol 90 (5) ◽  
pp. 2195-2207 ◽  
Author(s):  
Maria Fernanda de Castro-Amarante ◽  
Cynthia A. Pise-Masison ◽  
Katherine McKinnon ◽  
Robyn Washington Parks ◽  
Veronica Galli ◽  
...  
Keyword(s):  
T Cells ◽  
Leukemia Virus ◽  
Receptor Expression ◽  
Monocyte Subsets ◽  
Viral Dna ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Classical Monocytes ◽  
Intermediate Monocytes

ABSTRACTBecause the viral DNA burden correlates with disease development, we investigated the contribution of monocyte subsets (classical, intermediate, and nonclassical monocytes) to the total viral burden in 22 human T cell leukemia virus type 1 (HTLV-1)-infected individuals by assessing their infectivity status, frequency, as well as chemotactic and phagocytic functions. All three monocyte subsets sorted from HTLV-1-infected individuals were positive for viral DNA, and the frequency of classical monocytes was lower in the blood of HTLV-1-infected individuals than in that of uninfected individuals, while the expression levels of the chemokine receptors CCR5, CXCR3, and CX3CR1 in classical monocytes were higher in HTLV-1-infected individuals than uninfected individuals; the percentage of intermediate monocytes and their levels of chemokine receptor expression did not differ between HTLV-1-infected and uninfected individuals. However, the capacity of intermediate monocytes to migrate to CCL5, the ligand for CCR5, was higher, and a higher proportion of nonclassical monocytes expressed CCR1, CXCR3, and CX3CR1. The level of viral DNA in the monocyte subsets correlated with the capacity to migrate to CCL2, CCL5, and CX3CL1 for classical monocytes, with lower levels of phagocytosis for intermediate monocytes, and with the level of viral DNA in CD8+and CD4+T cells for nonclassical monocytes. These data suggest a model whereby HTLV-1 infection augments the number of classical monocytes that migrate to tissues and become infected and the number of infected nonclassical monocytes that transmit virus to CD4+and CD8+T cells. These results, together with prior findings in a macaque model of HTLV-1 infection, support the notion that infection of monocytes by HTLV-1 is likely a requisite for viral persistence in humans.IMPORTANCEMonocytes have been implicated in immune regulation and disease progression in patients with HTLV-1-associated inflammatory diseases. We detected HTLV-1 DNA in all three monocyte subsets and found that infection impacts surface receptor expression, migratory function, and subset frequency. The frequency of nonclassical patrolling monocytes is increased in HTLV-1-infected individuals, and they have increased expression of CCR1, CXCR3, and CX3CR1. The viral DNA level in nonclassical monocytes correlated with the viral DNA level in CD4+and CD8+T cells. Altogether, these data suggest an increased recruitment of classical monocytes to inflammation sites that may result in virus acquisition and, in turn, facilitate virus dissemination and viral persistence. Our findings thus provide new insight into the importance of monocyte infection in viral spread and suggest targeting of monocytes for therapeutic intervention.

scholarly journals Monocytes of Different Subsets in Complexes with Platelets in Patients with Myocardial Infarction

2018 ◽  
Vol 118 (11) ◽  
pp. 1969-1981 ◽  
Author(s):  
Marina Loguinova ◽  
Natalia Pinegina ◽  
Valeria Kogan ◽  
Murad Vagida ◽  
Anush Arakelyan ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Annexin V ◽  
Published Data ◽  
Healthy Controls ◽  
New Information ◽  
Platelet Antigen ◽  
Classical Monocytes ◽  
Intermediate Monocytes

AbstractAcute myocardial infarction (AMI) is associated with activation of various cells, including platelets that form monocyte–platelet complexes (MPCs). Here, we analysed MPC in vivo and in vitro and investigated the abilities of different monocyte subclasses to form MPC, the characteristics of the cells involved in MPC formation and MPC changes in AMI. We identified MPC by co-staining for platelet antigen CD41a and monocyte antigens CD14 and CD16. Platelet activation was evaluated from expression of phosphatidylserine as revealed by annexin V. Our results confirm published data and provide new information regarding the patterns of MPC in AMI patients. We found that the patterns of platelet aggregation with monocytes were different in AMI patients and controls: (1) in AMI patients, MPC formed by intermediate monocytes carry more platelets whereas in healthy controls more platelets aggregated with classical monocytes; (2) the numbers of MPC in AMI patients, being already higher than in controls, were further increased if these patients suffered various in-hospital complications; (3) on the basis of the CD41a fluorescence of the antibody-stained MPC, some of the aggregates seem to consist of monocytes and platelet-derived extracellular vesicles (EVs); (4) aggregation of monocytes with platelet EV occurred in in vitro experiments; and (5) these experiments demonstrated that monocytes from AMI patients aggregate with both platelets and platelet EVs more efficiently than do monocytes from controls. MPC in AMI patients may play an important role in this pathology.

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 Relationship between dynamic changes in subpopulations of blood monocytes and the development of complications in patients with acute myocardial infarction

2020 ◽  
Vol 27 (4) ◽  
pp. 9-17
Author(s):  
T. V. Talayeva ◽  
O. M. Parkhomenko ◽  
I. V. Tretyak ◽  
O. V. Dovhan ◽  
O. V. Shumakov
Keyword(s):  
Myocardial Infarction ◽  
Absolute Number ◽  
Control Group ◽  
Blood Monocytes ◽  
The Absolute ◽  
Anti Inflammatory ◽  
Classical Monocytes ◽  
Intermediate Monocytes ◽  
Patrolling Monocytes

The aim – to determine the extent of different subpopulations of blood monocytes in acute myocardial infarction (AMI) with ST-segment elevation patients on day 1 and 7 and to evaluate the relationship between their content and the dynamics of changes and the risk of complications after AMI.Materials and methods. The composition of individual subpopulations of monocytes in the peripheral venous blood (and general clinical and biochemical blood tests) was evaluated in 50 pts with STEMI (who were admitted within 6 hours after the onset of the disease) at admission (before primary PCI) and on day 7. All patients received standard recommended therapy. Dynamic heart echocardiography was also performed on the 1st and 7th day. All patients were divided into 2 groups depending on the dynamical increase (1 group – 21 pts) or decrease (2 group – 29 pts) of classical monocytes (CD14hiCD16–) subpopulation during 7 days of follow-up. The control group included 15 healthy subjects with no signs of coronary heart disease and 23 pts with chronic coronary heart disease without AMI.Results and discussion. In subgroup 1, the percentage of the «classical» fraction of monocytes during the observation increased to 89.0±1.2 %, which was 4.2 % more than on the 1st day and 12.5 % more than in the control group (р<0.05), while the absolute amount of classic monocytes on day 7 increased by 48 % compared to initial value (р<0.01). The percentage of «intermediate» (CD14hiCD16+) blood monocytes in patients of this subgroup on the 1st day of hospitalization was 70 % higher than in the control group, and 42 % higher than in the 2nd subgroup of patients (р<0,001), however, on the 7th day it decreased by 30 % compared to baseline, although it remained by 8 % more than in the control group (the absolute number of «intermediate» monocytes did not change). The activation index (IA) of the «intermediate» monocytes on the first day did not differ between subgroups and was 40 % higher than in the control group (р<0.001). However, in the dynamics of observation, in patients of subgroup 1, this figure did not change, while in subgroup 2 IA decreased by 60 % (р<0.001). Despite the fact that the absolute number of anti-inflammatory («patrolling») (CD14+lowCD16++) monocytes did not change until the 7th day of observation (and their percentage decreased slightly), their IA was significantly lower than in the control group (95 %) and in patients of subgroup 2 (92 %, р<0,001). In patients of subgroup 2, the decrease of the percentage of «classic» monocytes was –7.7 % (from 90.4±0.8 to 83.4±1.2 %). Despite the fact that the number and percentage of intermediate monocytes increased in dynamics, their IA decreased almost 2 times, which may indicate a decrease in the pro-inflammatory ability these monocytes. The percentage and number of «patrolling» monocytes increased in dynamics by 37.4 % (р<0.0001) and by 268.3 % (р<0.01), respectively. IA of patrolling monocytes was almost 12 and 7 times higher than in patients of subgroup 1 on the 1st and 7th day of observation, respectively, which may indicate a significant activation of anti-inflammatory activity of patrolling monocytes. Intracardiac thrombosis was 3.3 times more common in patients of subgroup 1, in this subgroup was also more often noted (compared to the subgroup 2): dilatation of the left ventricle (almost 8 times), reduction of left ventricular ejection fraction (4 times), and pathological post-infarction remodeling of the left ventricle (almost 7 times).Conclusions. The results of the study indicate the important role of different subpopulations of blood monocytes in the processes of myocardial damage and recovery (in particular, the pro-inflammatory role of increasing the number of classical monocytes and increasing the activity of intermediate monocytes, as well as the anti-inflammatory role of increasing the number, percentage and activity of patrolling monocytes) in patients with AMI and can be the basis for developing new approaches to the diagnosis and prevention of complications of this disease.

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