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https://www.readbyqxmd.com/read/29670076/cathelicidins-prime-platelets-to-mediate-arterial-thrombosis-and-tissue-inflammation
#1
Joachim Pircher, Thomas Czermak, Andreas Ehrlich, Clemens Eberle, Erik Gaitzsch, Andreas Margraf, Jochen Grommes, Prakash Saha, Anna Titova, Hellen Ishikawa-Ankerhold, Konstantin Stark, Tobias Petzold, Thomas Stocker, Ludwig T Weckbach, Julia Novotny, Markus Sperandio, Bernhard Nieswandt, Alberto Smith, Hanna Mannell, Barbara Walzog, David Horst, Oliver Soehnlein, Steffen Massberg, Christian Schulz
Leukocyte-released antimicrobial peptides contribute to pathogen elimination and activation of the immune system. Their role in thrombosis is incompletely understood. Here we show that the cathelicidin LL-37 is abundant in thrombi from patients with acute myocardial infarction. Its mouse homologue, CRAMP, is present in mouse arterial thrombi following vascular injury, and derives mainly from circulating neutrophils. Absence of hematopoietic CRAMP in bone marrow chimeric mice reduces platelet recruitment and thrombus formation...
April 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29643232/increased-neutrophil-extracellular-trap-formation-promotes-thrombosis-in-myeloproliferative-neoplasms
#2
Ofir Wolach, Rob S Sellar, Kimberly Martinod, Deya Cherpokova, Marie McConkey, Ryan J Chappell, Alexander J Silver, Dylan Adams, Cecilia A Castellano, Rebekka K Schneider, Robert F Padera, Daniel J DeAngelo, Martha Wadleigh, David P Steensma, Ilene Galinsky, Richard M Stone, Giulio Genovese, Steven A McCarroll, Bozenna Iliadou, Christina Hultman, Donna Neuberg, Ann Mullally, Denisa D Wagner, Benjamin L Ebert
Thrombosis is a major cause of morbidity and mortality in Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), clonal disorders of hematopoiesis characterized by activated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling. Neutrophil extracellular trap (NET) formation, a component of innate immunity, has been linked to thrombosis. We demonstrate that neutrophils from patients with MPNs are primed for NET formation, an effect blunted by pharmacological inhibition of JAK signaling...
April 11, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29609040/clinico-hematological-profile-and-thrombotic-hemorrhagic-events-in-150-chinese-patients-with-essential-thrombocythemia
#3
Dian Zhou, Wei Chen, Hai Cheng, Jian-Lin Qiao, Li-Li Zhu, Zhen-Yu Li, Kai-Lin Xu
Essential thrombocythemia (ET) is an uncommon chronic myeloproliferative disorder with no cure. Patients with ET are at risk of different complications, and currently there are no optimal prognostic standards to predict severe post-diagnosis complications such as thrombosis and hemorrhage. In this study, we retrospectively analyzed the full set of clinical data from 150 Chinese patients with ET enrolled from 2013 to 2016. We discovered that neutrophil-to-lymphocyte ratio (NLR), along with other known clinical parameters such as age, leukocyte count, incidence of thrombotic events is higher in patients with JAK2 V617F mutation...
March 27, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29608758/neutrophil-extracellular-trap-release-is-associated-with-antinuclear-antibodies-in-systemic-lupus-erythematosus-and-anti-phospholipid-syndrome
#4
Maarten van der Linden, Lucas L van den Hoogen, Geertje H A Westerlaken, Ruth D E Fritsch-Stork, Joël A G van Roon, Timothy R D J Radstake, Linde Meyaard
Objectives: Increased release of neutrophil extracellular traps (NETs) is implicated in the activation of plasmacytoid dendritic cells, vascular disease and thrombosis in SLE and APS. However, studies comparing NET release between patients with SLE and APS are lacking. Here we evaluated plasma-induced NET release in a large cohort of patients with SLE, SLE + APS and primary APS in relation to clinical and serological parameters. Methods: Neutrophils from healthy controls were exposed to plasma of heterologous healthy controls (n = 27) or SLE (n = 55), SLE + APS (n = 38) or primary APS (PAPS) (n = 28) patients and NET release was quantified by immunofluorescence...
March 28, 2018: Rheumatology
https://www.readbyqxmd.com/read/29584534/the-pro-inflammatory-role-of-platelets-in-cancer
#5
A K Olsson, J Cedervall
Thrombosis is a frequent issue in cancer patients. Tumor-induced platelet activation and coagulation does not only constitute a significant risk for thrombosis, but also contribute to tumor progression by promoting critical processes such as angiogenesis and metastasis. In addition to their role in hemostasis, platelets are increasingly recognized as regulators of inflammation. By modulating the immune system, platelets regulate several aspects of cancer-associated pathology. Platelets influence the inflammatory response in cancer by affecting the activation status of the endothelium and by recruiting leukocytes to primary and metastatic tumor sites, as well as to distant organs unaffected by tumor growth...
March 27, 2018: Platelets
https://www.readbyqxmd.com/read/29572206/roles-of-pad4-and-netosis-in-experimental-atherosclerosis-and-arterial-injury-implications-for-superficial-erosion
#6
Grégory Franck, Thomas L Mawson, Eduardo J Folco, Roberto Molinaro, Victoria Ruvkun, Daniel Engelbertsen, Xin Liu, Yevgenia Tesmenitsky, Eugenia Shvartz, Galina K Sukhova, Jean-Baptiste Michel, Antonino Nicoletti, Andrew H Lichtman, Denisa D Wagner, Kevin J Croce, Peter Libby
<u>Rationale:</u> Neutrophils likely contribute to the thrombotic complications of human atheromata. In particular, neutrophil extracellular traps (NETs) could exacerbate local inflammation and amplify and propagate arterial intimal injury and thrombosis. Peptidyl arginine deiminase 4 (PAD4) participates in NET formation, but understanding of this enzyme's role in atherothrombosis remains scant. <u>Objective:</u> This study tested the hypothesis that PAD4 and NETs influence experimental atherogenesis and in processes implicated in superficial erosion, a form of plaque complication we previously associated with NETs...
March 23, 2018: Circulation Research
https://www.readbyqxmd.com/read/29569402/use-of-neutrophil-lymphocyte-ratio-for-risk-stratification-and-relationship-with-time-in-therapeutic-range-in-patients-with-nonvalvular-atrial-fibrillation-a-pilot-study
#7
Kahraman Cosansu, Mehmet Bulent Vatan, Huseyin Gunduz, Ramazan Akdemir
BACKGROUND: Atrial fibrillation is one of the most common abnormal heart rhythms. Neutrophil-lymphocyte ratio (NLR) has emerged as a potential marker for the level of inflammation in cardiac disorders. HYPOTHESIS: NLR might be associated with thrombosis and bleeding risk scores and might predict cardioembolic risk in nonvalvular atrial fibrillation (NVAF) patients within the therapeutic international normalized ratio (INR). METHODS: We enrolled 272 patients taking warfarin for NVAF and classified them into 2 groups: Group A consisted of patients (n = 132) whose time in therapeutic range (TTR) was ≥65%, and Group B comprised patients (n = 139) whose TTR was <65%...
March 22, 2018: Clinical Cardiology
https://www.readbyqxmd.com/read/29563120/platelet-hmgb1-is-required-for-efficient-bacterial-clearance-in-intra-abdominal-bacterial-sepsis-in-mice
#8
Hui Zhou, Meihong Deng, Yingjie Liu, Chenxuan Yang, Rosemary Hoffman, Jingjiao Zhou, Patricia A Loughran, Melanie J Scott, Matthew D Neal, Timothy R Billiar
Thrombocytopenia impairs host defense and hemostasis in sepsis. However, the mechanisms of how platelets regulate host defense are not fully understood. High-mobility group box 1 (HMGB1), a danger-associated molecular pattern protein, is released during infection and contributes to the pathogenesis of sepsis. Platelets express HMGB1, which is released on activation and has been shown to play a critical role in thrombosis, monocyte recruitment, and neutrophil extracellular trap (NET) production. However, the contribution of platelet HMGB1 to host defense is unknown...
March 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29529237/phosphatidylserine-on-microparticles-and-associated-cells-contributes-to-the-hypercoagulable-state-in-diabetic-kidney-disease
#9
Muxin Yu, Rujuan Xie, Yan Zhang, Hui Liang, Li Hou, Chengyuan Yu, Jinming Zhang, Zengxiang Dong, Ye Tian, Yayan Bi, Junjie Kou, Valerie A Novakovic, Jialan Shi
Background: Relatively little is known about the role of phosphatidylserine (PS) in procoagulant activity (PCA) in patients with diabetic kidney disease (DKD). This study was designed to evaluate whether exposed PS on microparticles (MPs) and MP-origin cells were involved in the hypercoagulability in DKD patients. Methods: DKD patients (n = 90) were divided into three groups based on urinary albumin excretion rate, defined as normoalbuminuria (No-A) (<30 mg/24 h), microalbuminuria (Mi-A) (30-299 mg/24 h) or macroalbuminuria (Ma-A) (>300 mg/24 h), and compared with healthy controls (n = 30)...
February 26, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29520957/quantification-of-nets-associated-markers-by-flow-cytometry-and-serum-assays-in-patients-with-thrombosis-and-sepsis
#10
K H Lee, L Cavanaugh, H Leung, F Yan, Z Ahmadi, B H Chong, F Passam
INTRODUCTION: Neutrophil extracellular traps (NETs) are networks of extracellular fibres produced from neutrophil DNA with a pathogenic role in infection, thrombosis and other conditions. Reliable assays for measuring NETs are desirable as novel treatments targeting NETs are being explored for the treatment of these conditions. We compare a whole blood flow cytometry method with serum assays to measure NETs-associated markers in patients with sepsis and thrombosis. METHODS: Patients with deep venous thrombosis (n = 25), sepsis (n = 21) and healthy controls (n = 23) were included in the study...
March 9, 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29501579/chondroitin-sulfate-protects-vascular-endothelial-cells-from-toxicities-of-extracellular-histones
#11
Fumihiko Nagano, Tomohiro Mizuno, Shuji Mizumoto, Kengo Yoshioka, Kazuo Takahashi, Naotake Tsuboi, Shoichi Maruyama, Shuhei Yamada, Tadashi Nagamatsu
Extracellular histones induce lethal thrombosis by promoting platelet aggregation, neutrophil migration, and cell injuries. Heparin, which has negative charges, can bind to extracellular histones; however, heparin strongly inhibits the activation of coagulation. Since chondroitin sulfate (CS) shows less effect on the coagulation system than heparin does, CS has the potential to become an effective drug for lethal thrombosis with high risk of bleeding. To elucidate the therapeutic mechanisms of CS in lethal thrombosis, we investigated the interaction between CS and extracellular histones...
February 28, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29482566/predictive-value-of-neutrophil-to-lymphocyte-ratio-and-platelet-to-lymphocyte-ratio-for-acute-deep-vein-thrombosis-after-total-joint-arthroplasty-a-retrospective-study
#12
Chen Yao, Zhe Zhang, Yao Yao, Xingquan Xu, Qing Jiang, Dongquan Shi
BACKGROUND: Deep vein thrombosis (DVT) is a common and severe complication of total joint arthroplasty (TJA). Inflammation has been proved to play a role in DVT. The neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) are biomarkers for systemic inflammation. The aim of the study is to investigate the predictive value of NLR and PLR for acute TJA-induced DVT. METHOD: A total of 773 patients who underwent primary TJA in our hospital were included in this retrospective study...
February 27, 2018: Journal of Orthopaedic Surgery and Research
https://www.readbyqxmd.com/read/29482157/il-17a-promotes-the-formation-of-deep-vein-thrombosis-in-a-mouse-model
#13
Peiwu Ding, Shaoshao Zhang, Miao Yu, Yuqian Feng, Qi Long, Huimin Yang, Jingdong Li, Min Wang
Deep venous thrombosis (DVT) is a significant problem in the health care industry worldwide. However, the factors and signaling pathways that trigger DVT formation are still largely unknown. In this study, we investigated the role of interleukin-17A (IL-17A) in DVT formation, focusing on the role of platelet aggregation, neutrophil infiltration, and endothelium cell (EC) activation. Notably, IL-17A levels increased in DVT patients as well as in a mouse DVT model. The DVT model mice were injected with recombinant mouse-IL-17A (rIL-17A) or anti-IL-17A monoclonal antibody (mAb) to further evaluate the effects of this cytokine...
February 23, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29474368/circulating-extracellular-dna-is-an-independent-predictor-of-mortality-in-elderly-patients-with-venous-thromboembolism
#14
Miguel Jiménez-Alcázar, Andreas Limacher, Rachita Panda, Marie Méan, Josephine Bitterling, Sven Peine, Thomas Renné, Jürg H Beer, Drahomir Aujesky, Bernhard Lämmle, Tobias A Fuchs
BACKGROUND: Venous thromboembolism (VTE) is a major cause of morbidity and mortality in elderly patients. Extracellular DNA is a pro-inflammatory and pro-thrombotic mediator in vitro and in animal models. Levels of circulating extracellular DNA (ceDNA) are increased in VTE patients, but the association of ceDNA with VTE extent and clinical outcome is poorly understood. OBJECTIVES: We analyzed the association of ceDNA with the extent of VTE, categorized as distal and proximal deep vein thrombosis and pulmonary embolism, and with the clinical outcomes VTE recurrence and mortality...
2018: PloS One
https://www.readbyqxmd.com/read/29467851/proteinase-3-expression-on-the-neutrophils-of-patients-with-paroxysmal-nocturnal-hemoglobinuria
#15
Hui Liu, Yi Liu, Yi Li, Zhaoyun Liu, Liyan Li, Shaoxue Ding, Yihao Wang, Tian Zhang, Lijuan Li, Zonghong Shao, Rong Fu
Proteinase 3 (PR3) is released from neutrophils and regulates platelet activity, which is associated with cluster of differentiation (CD)177 antigen (NB1), a glycosylphosphatidylinositol-linked protein. In the present study, the effect of PR3 on thrombosis in paroxysmal nocturnal hemoglobinuria (PNH) and PNH-aplastic anemia (AA) syndrome was explored. The expression of PR3 and NB1 on CD59- neutrophils was detected by flow cytometry, immunofluorescence (IF), reverse transcription-quantitative polymerase chain reaction analysis and western blotting...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29444200/loss-of-sirt3-accelerates-arterial-thrombosis-by-increasing-formation-of-neutrophil-extracellular-traps-and-plasma-tissue-factor-activity
#16
Daniel S Gaul, Julien Weber, Lambertus J Van Tits, Susanna Sluka, Lisa Pasterk, Martin F Reiner, Natacha Calatayud, Christine Lohmann, Roland Klingenberg, Jürgen Pahla, Daria Vdovenko, Felix C Tanner, Giovanni G Camici, Urs Eriksson, Johan Auwerx, François Mach, Stephan Windecker, Nicolas Rodondi, Thomas F L Uuml Scher, Stephan Winnik, Christian M Matter
BACKGROUND: Sirtuin 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 Results: Using 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+/+ wildtype (WT, n = 8, p<0...
February 10, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29438080/thrombus-neutrophil-extracellular-traps-content-impair-tpa-induced-thrombolysis-in-acute-ischemic-stroke
#17
Celina Ducroux, Lucas Di Meglio, Stephane Loyau, Sandrine Delbosc, William Boisseau, Catherine Deschildre, Malek Ben Maacha, Raphael Blanc, Hocine Redjem, Gabriele Ciccio, Stanislas Smajda, Robert Fahed, Jean-Baptiste Michel, Michel Piotin, Laurence Salomon, Mikael Mazighi, Benoit Ho-Tin-Noe, Jean-Philippe Desilles
BACKGROUND AND PURPOSE: Neutrophil Extracellular Traps (NETs) are DNA extracellular networks decorated with histones and granular proteins produced by activated neutrophils. NETs have been identified as major triggers and structural factors of thrombosis. A recent study designated extracellular DNA threads from NETs as a potential therapeutic target for improving tissue-type plasminogen activator (tPA)-induced thrombolysis in acute coronary syndrome. The aim of this study was to assess the presence of NETs in thrombi retrieved during endovascular therapy in patients with acute ischemic stroke (AIS) and their impact on tPA-induced thrombolysis...
February 8, 2018: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29428537/neutrophil-to-lymphocyte-ratio-and-platelet-to-lymphocyte-ratio-are-effective-predictors-of-prognosis-in-patients-with-acute-mesenteric-arterial-embolism-and-thrombosis-short-title-nlr-plr-predict-the-prognosis-of-amae-amat
#18
Shuai Wang, Han Liu, Qi Wang, Zhihua Cheng, Siqiao Sun, Yang Zhang, Xiwei Sun, Zhongying Wang, Liqun Ren
BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been shown to be valuable prognostic markers for a variety of pathological conditions including solid tumors, sepsis and others. However, the prognostic values of the NLR and PLR in patients with acute mesenteric arterial embolism (AMAE) and acute mesenteric arterial thrombosis (AMAT) have not been elucidated. The aim of this study was to determine the predictive value of the NLR and PLR for poor prognosis in patients with AMAE and AMAT...
February 8, 2018: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/29404659/the-phenomenon-of-neutrophil-extracellular-traps-in-vascular-diseases
#19
REVIEW
Dorota Dąbrowska, Ewa Jabłońska, Marzena Garley, Jolanta Sawicka-Powierza, Karolina Nowak
Vascular diseases constitute a global health issue due to the increasing number of cases of patients with these diseases. The pathogenesis of the majority of these diseases, including atherosclerosis and thrombosis, is complex and not yet fully understood. One of the major causes for their occurrence can be immune disorders resulting in the development of a chronic inflammation within the vessels. In recent years, studies have placed emphasis on the role of neutrophils in the development of these diseases, i...
February 5, 2018: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/29399517/neutrophil-extracellular-traps-are-increased-in-cancer-patients-but-does-not-associate-with-venous-thrombosis
#20
Rahmi Oklu, Rahul A Sheth, Keith H K Wong, Amin H Jahromi, Hassan Albadawi
Background: A single center, prospective tissue-based study was conducted to investigate an association between neutrophil extracellular traps (NETs) and venous thromboembolic disease in patients with malignancy. Methods: Plasma was collected from 65 patients in which 27 were cancer patients and 38 were age-matched non-cancer patients. Plasma NETs, circulating free DNA (cfDNA), DNase-1, endonuclease-G, endonuclease activity and thrombin-antithrombin III (TAT) complex levels was quantified...
December 2017: Cardiovascular Diagnosis and Therapy
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