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https://www.readbyqxmd.com/read/29444200/loss-of-sirt3-accelerates-arterial-thrombosis-by-increasing-formation-of-neutrophil-extracellular-traps-and-plasma-tissue-factor-activity
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/29391581/panton-valentine-leukocidin-associated-with-s-aureus-osteomyelitis-activates-platelets-via-neutrophil-secretion-products
#6
Silke Niemann, Anne Bertling, Martin F Brodde, Anke C Fender, Hélène Van de Vyver, Muzaffar Hussain, Dirk Holzinger, Dirk Reinhardt, Georg Peters, Christine Heilmann, Bettina Löffler, Beate E Kehrel
Globalization and migration promote the spread of Panton-Valentine leukocidin (PVL)-positive Staphylococcus aureus strains. The toxin PVL is linked to the development of thrombosis in association with osteomyelitis. The mechanisms by which PVL drives thrombosis development are however still unknown. We demonstrate that PVL-damaged neutrophils activate platelets via neutrophil secretion products, such as α-defensins and the myeloperoxidase product HOCl, as well as the formation of HOCl-modified proteins. Neutrophil damage by PVL is blocked by anti-PVL-antibodies, explaining why especially young osteomyelitis patients with a low antibody titre against PVL suffer from thrombotic complications...
February 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29391442/deep-vein-thrombosis-in-mice-is-regulated-by-platelet-hmgb1-through-release-of-neutrophil-extracellular-traps-and-dna
#7
Mitchell R Dyer, Qiwei Chen, Shannon Haldeman, Hamza Yazdani, Rosemary Hoffman, Patricia Loughran, Allan Tsung, Brian S Zuckerbraun, Richard L Simmons, Matthew D Neal
Venous thromboembolic (VTE) disease, consisting of deep venous thrombosis (DVT) and pulmonary embolism (PE) is a leading cause of morbidity and mortality. Current prophylactic measures are insufficient to prevent all occurrence in part due to an incomplete understanding of the underlying pathophysiology. Mounting evidence describes interplay between activation of the innate immune system and thrombus development. Recent work has demonstrated that platelet release of HMGB1 leads to increased microvascular complications following injury...
February 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29386829/histopathologic-finding-of-perieschar-lesions-in-tsutsugamushi-disease-shows-lymphocytic-vasculitis-mimicking-angiocentric-lymphoma
#8
Min Soo Jang, Jong Bin Park, Kang Hoon Lee, Ji Yun Jang, Myeong Hyeon Yang, Joon Hee Kim, Hyun Hwangbo, Taek Geun Lee, Kee Suck Suh
Background: Tsutsugamushi disease is an acute, febrile, infectious disease caused by Orientia tsutsugamushi. Several studies investigating the histopathologic findings of eschars in tsutsugamushi disease reported leukocytoclastic vasculitis and neutrophil infiltration as the major findings. However, these findings may result from secondary changes following tissue necrosis. The histopathologic findings of perieschar lesions may be important to understand the primary changes associated with tsutsugamushi disease...
February 2018: Annals of Dermatology
https://www.readbyqxmd.com/read/29382950/neutrophils-and-neutrophil-extracellular-traps-in-the-liver-and-gastrointestinal-system
#9
REVIEW
Masaki Honda, Paul Kubes
Neutrophil extracellular traps (NETs) have an important role during infection by helping neutrophils to capture and kill pathogens. However, evidence is accumulating that uncontrolled or excessive production of NETs is related to the exacerbation of inflammation and the development of autoimmunity, cancer metastasis and inappropriate thrombosis. In this Review, we focus on the role of NETs in the liver and gastrointestinal system, outlining their protective and pathological effects. The latest mechanistic insights in NET formation, interactions between microorganisms and NETs and the relationship between neutrophil subtypes and their functions are also discussed...
January 31, 2018: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29373226/multiple-cerebral-infarctions-due-to-patent-foramen-ovale-in-a-patient-with-eosinophilic-granulomatosis-with-polyangiitis
#10
Kota Maekawa, Masunari Shibata, Masaru Seguchi, Kazuto Kobayashi, Yutaka Naito, Fumitaka Miya
A 51-year-old man was diagnosed with eosinophilic granulomatosis with polyangiitis 6 years ago due to asthma, sinusitis, hypereosinophilia, and peripheral neuropathy based on the diagnostic criteria of American College of Rheumatology, and corticosteroid therapy achieved a remission. One year ago, he was hospitalized due to deep venous thrombosis (DVT) and pulmonary embolism, and rivaroxaban was administrated. He was admitted to our hospital for acute onset of diplopia and right hemiparesis. Peripheral blood examinations disclosed leukocytosis with hypereosinophilia...
January 17, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/29371565/innate-and-adaptive-immunity-to-mucorales
#11
REVIEW
Harlene Ghuman, Kerstin Voelz
Mucormycosis is an invasive fungal infection characterised by rapid filamentous growth, which leads to angioinvasion, thrombosis, and tissue necrosis. The high mortality rates (50-100%) associated with mucormycosis are reflective of not only the aggressive nature of the infection and the poor therapeutics currently employed, but also the failure of the human immune system to successfully clear the infection. Immune effector interaction with Mucorales is influenced by the developmental stage of the mucormycete spore...
September 5, 2017: Journal of Fungi (Basel, Switzerland)
https://www.readbyqxmd.com/read/29332224/phosphatidylserine-exposing-blood-and-endothelial-cells-contribute-to-the-hypercoagulable-state-in-essential-thrombocythemia-patients
#12
Dongxia Tong, Muxin Yu, Li Guo, Tao Li, Jihe Li, Valerie A Novakovic, Zengxiang Dong, Ye Tian, Junjie Kou, Yayan Bi, Jinghua Wang, Jin Zhou, Jialan Shi
The mechanisms of thrombogenicity in essential thrombocythemia (ET) are complex and not well defined. Our objective was to explore whether phosphatidylserine (PS) exposure on blood cells and endothelial cells (ECs) can account for the increased thrombosis and distinct thrombotic risks among mutational subtypes in ET. Using flow cytometry and confocal microscopy, we found that the levels of PS-exposing erythrocytes, platelets, leukocytes, and serum-cultured ECs were significantly higher in each ET group [JAK2, CALR, and triple-negative (TN) (all P < 0...
January 13, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29325504/platelet-to-lymphocyte-ratio-neutrophil-to-lymphocyte-ratio-and-platelet-indices-in-patients-with-acute-deep-vein-thrombosis
#13
Liang Ming, Zhiyun Jiang, Junfen Ma, Qian Wang, Fan Wu, Jiedan Ping
BACKGROUND: Inflammation is associated with an increased risk of thrombotic events and complete blood count (CBC) is an easily measured test. The purpose of this study was to evaluate the value of CBC relative parameters including mean platelet volume (MPV), platelet-to-lymphocyte ratio (PLR), mean platelet volume-to-lymphocyte ratio (MPVLR), and neutrophil-to-lymphocyte ratio (NLR) for patients with acute deep vein thrombosis (DVT). PATIENTS AND METHODS: A total of 115 patients with unprovoked DVT of the lower extremities and 105 controls were recruited in this study...
January 12, 2018: VASA. Zeitschrift Für Gefässkrankheiten
https://www.readbyqxmd.com/read/29325226/citrullinated-histone-h3-a-biomarker-of-neutrophil-extracellular-trap-formation-predicts-the-risk-of-venous-thromboembolism-in-cancer-patients
#14
Lisa-Marie Mauracher, Florian Posch, Kimberly Martinod, Ella Grilz, Thomas Däullary, Lena Hell, Christine Brostjan, Christoph Zielinski, Cihan Ay, Denisa D Wagner, Ingrid Pabinger, Johannes Thaler
BACKGROUND: Neutrophil extracellular traps (NETs) are decondensed chromatin fibers which might play a role in the prothrombotic state of cancer patients. OBJECTIVES: Here we investigated whether citrullinated histone H3 (H3Cit), a biomarker for NET formation, cell-free DNA (cfDNA), and nucleosomes predict venous thromboembolism (VTE) in cancer patients. PATIENTS/METHODS: Nine-hundred-forty-six patients with newly-diagnosed cancer or progression after remission were enrolled in this prospective observational cohort study...
January 11, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29306575/mouse-models-of-cancer-associated-thrombosis
#15
Yohei Hisada, Nigel Mackman
Cancer patients have an increased risk of venous thromboembolism (VTE) compared with the general population. Mouse models are used to better understand the mechanisms of cancer-associated thrombosis. Several mouse models of cancer-associated thrombosis have been developed that use different mouse strains, tumors, tumor sites and thrombosis models. In this review, we summarize these different models. These models have been used to determine the role of different pathways in cancer-associated thrombosis. For instance, they have revealed roles for tumor-derived tissue factor-positive microvesicles and neutrophil extracellular traps in thrombosis in tumor-bearing mice...
December 29, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/29304522/the-pathophysiological-role-of-neutrophil-extracellular-traps-in-inflammatory-diseases
#16
Aldo Bonaventura, Luca Liberale, Federico Carbone, Alessandra Vecchié, Candela Diaz-Cañestro, Giovanni G Camici, Fabrizio Montecucco, Franco Dallegri
Neutrophil pathogen-killing mechanism termed neutrophil extracellular traps (NETs) has been recently identified. NETs consist of chromatin and histones along with serine proteases and myeloperoxidase and are induced by a great variety of infectious and non-infectious stimuli . NETosis is a kind of programmed neutrophil death characterized by chromatin decondensation and release of nuclear granular contents, mainly driven by peptidylarginine deiminase 4 citrullination of histones. Although classically related to the protection against infectious pathogens, nowadays NETs have been described as a player of several pathophysiological processes...
January 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29275396/variant-of-lemierre-s-syndrome-with-internal-jugular-vein-aneurysm
#17
Siew Houy Chua, Sidney Ching Liang Ong, Yuan Hwen Liew
Internal jugular vein (IJV) aneurysm is a rare entity, and a thrombosed aneurysm poses diagnostic and management challenges. We came across a 53-year-old woman who presented with fever, vomiting and right neck swelling for a week. Laboratory investigations showed neutrophilic leucocytosis, raised acute phase reactant and blood culture yielded Klebsiella pneumoniae Ultrasound and contrast-enhanced CT neck revealed a large fusiform aneurysm of the right IJV with filling defect extending from the aneurysm into the right transverse sinus...
December 22, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/29246924/the-prothrombotic-state-in-paroxysmal-nocturnal-hemoglobinuria-a-multifaceted-source
#18
REVIEW
Barnaby Peacock-Young, Fraser L Macrae, Darren J Newton, Anita Hill, Robert A S Ariëns
Paroxysmal nocturnal hemoglobinuria is a rare acquired hematologic disorder, the most serious complication of which is thrombosis. The increased incidence of thrombosis in paroxysmal nocturnal hemoglobinuria is still poorly understood, but unlike many other thrombotic disorders, predominantly involves complement-mediated mechanisms. This review article discusses the different factors that contribute to the increased risk of thrombosis in paroxysmal nocturnal hemoglobinuria. Paroxysmal nocturnal hemoglobinuria leads to a complex and multifaceted prothrombotic state due to the pathological effects of platelet activation, intravascular hemolysis and neutrophil/monocyte activation...
January 2018: Haematologica
https://www.readbyqxmd.com/read/29236713/sirt3-deficiency-does-not-affect-venous-thrombosis-or-netosis-despite-mild-elevation-of-intracellular-ros-in-platelets-and-neutrophils-in-mice
#19
Hideki Hayashi, Deya Cherpokova, Kimberly Martinod, Thilo Witsch, Siu Ling Wong, Maureen Gallant, Stephen M Cifuni, Leonard P Guarente, Denisa D Wagner
Inflammation is a common denominator in chronic diseases of aging. Yet, how inflammation fuels these diseases remains unknown. Neutrophils are the primary leukocytes involved in the early phase of innate immunity and inflammation. As part of their anti-microbial defense, neutrophils form extracellular traps (NETs) by releasing decondensed chromatin lined with cytotoxic proteins. NETs have been shown to induce tissue injury and thrombosis. Here, we demonstrated that Sirt3, a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, an enzyme linked to human longevity, was expressed in mouse neutrophils and platelets...
2017: PloS One
https://www.readbyqxmd.com/read/29218045/factor-h-c-terminal-domains-are-critical-for-regulation-of-platelet-granulocyte-aggregate-formation
#20
Adam Z Blatt, Gurpanna Saggu, Claudio Cortes, Andrew P Herbert, David Kavanagh, Daniel Ricklin, John D Lambris, Viviana P Ferreira
Platelet/granulocyte aggregates (PGAs) increase thromboinflammation in the vasculature, and PGA formation is tightly controlled by the complement alternative pathway (AP) negative regulator, Factor H (FH). Mutations in FH are associated with the prothrombotic disease atypical hemolytic uremic syndrome (aHUS), yet it is unknown whether increased PGA formation contributes to the thrombosis seen in patients with aHUS. Here, flow cytometry assays were used to evaluate the effects of aHUS-related mutations on FH regulation of PGA formation and characterize the mechanism...
2017: Frontiers in Immunology
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