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Plasma Peptidylarginine Deiminase IV Promotes VWF-Platelet String Formation and Accelerates Thrombosis After Vessel Injury

Published on Aug 16, 2019in Circulation Research15.862
· DOI :10.1161/CIRCRESAHA.118.314571
Nicoletta Sorvillo10
Estimated H-index: 10
(Harvard University),
Daniella M. Mizurini1
Estimated H-index: 1
(Harvard University)
+ 11 AuthorsDenisa D. Wagner103
Estimated H-index: 103
(Harvard University)
Abstract
Rationale: PAD4 (peptidylarginine deiminase type IV), an enzyme essential for neutrophil extracellular trap formation (NETosis), is released together with neutrophil extracellular traps into the ex...
  • References (64)
  • Citations (4)
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References64
Newest
#1Maaike Schillemans (UvA: University of Amsterdam)H-Index: 3
#2Ellie Karampini (UvA: University of Amsterdam)H-Index: 3
Last. Ruben Bierings (UvA: University of Amsterdam)H-Index: 12
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textabstractSummary: The blood vessel wall has a number of self-healing properties, enabling it to minimize blood loss and prevent or overcome infections in the event of vascular trauma. Endothelial cells prepackage a cocktail of hemostatic, inflammatory and angiogenic mediators in their unique secretory organelles, the Weibel–Palade bodies (WPBs), which can be immediately released on demand. Secretion of their contents into the vascular lumen through a process called exocytosis enables the endo...
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#1Nara Aline Costa (UNESP: Sao Paulo State University)H-Index: 4
#2Ana Lúcia Gut (UNESP: Sao Paulo State University)H-Index: 10
Last. Marcos F. Minicucci (UNESP: Sao Paulo State University)H-Index: 21
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The objective of our study was to evaluate the association between peptidylarginine deiminase 4 (PAD4) concentration and its polymorphisms with mortality in patients with septic shock. We prospectively evaluated 175 patients aged over 18 years with septic shock upon intensive care unit (ICU) admission. However, 48 patients were excluded. Thus, 127 patients were enrolled in the study. At the time of the patients' enrollment, demographic information was recorded. Blood samples were taken within th...
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#1Venkatesh V. Nemmara (UMMS: University of Massachusetts Medical School)H-Index: 3
#2Ronak Tilvawala (UMMS: University of Massachusetts Medical School)H-Index: 4
Last. Paul R. Thompson (UMMS: University of Massachusetts Medical School)H-Index: 50
view all 7 authors...
Nicotinamide-N-methyltransferase (NNMT) catalyzes the irreversible methylation of nicotinamide (NAM) to form N-methyl nicotinamide using S-adenosyl methionine as a methyl donor. NNMT is implicated in several chronic disease conditions, including cancers, kidney disease, cardiovascular disease, and Parkinson’s disease. Although phosphorylation of NNMT in gastric tumors is reported, the functional effects of this post-translational modification has not been investigated. We previously reported tha...
4 CitationsSource
#1Yuki Maruchi (Aichi Medical University)H-Index: 1
#2Masanobu Tsuda (Aichi Medical University)H-Index: 17
Last. Naoshi Takeyama (Aichi Medical University)H-Index: 11
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Recent studies have suggested that excessive formation of neutrophil extracellular traps (NETs) plays a critical role in the pathogenesis of sepsis. Although elevation of the plasma level of cell-free DNA (cf-DNA) has been reported in sepsis patients, there has been little direct measurement of circulating free NETs such as myeloperoxidase-conjugated DNA (MPO-DNA). The objectives of this study were to detect NETs in the bloodstream of patients with septic shock, and to assess the correlations of...
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#1Junmei ChenH-Index: 16
#2Dominic W. Chung (UW: University of Washington)H-Index: 41
Increasing evidence indicates that inflammation can cause thrombosis by a von Willebrand factor (VWF)-mediated mechanism that includes endothelial activation, secretion of VWF, assembly of hyperadhesive VWF strings and fibers, cleavage by ADAMTS13, and adhesion and deposition of VWF-platelet thrombi in the vasculature. This mechanism appears to contribute to thrombosis not only in small vessels, but also in large vessels. Inflammation and VWF contribute to atherogenesis and may contribute to art...
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#1Ronak Tilvawala (UMMS: University of Massachusetts Medical School)H-Index: 4
#2Son Hong Nguyen (UMMS: University of Massachusetts Medical School)H-Index: 2
Last. Paul R. Thompson (UMMS: University of Massachusetts Medical School)H-Index: 50
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Summary Increased protein citrullination is linked to various diseases including rheumatoid arthritis (RA), lupus, and cancer. Citrullinated autoantigens, a hallmark of RA, are recognized by anti-citrullinated protein antibodies (ACPAs) which are used to diagnose RA. ACPA-recognizing citrullinated enolase, vimentin, keratin, and filaggrin are also pathogenic. Here, we used a chemoproteomic approach to define the RA-associated citrullinome. The identified proteins include numerous serine protease...
20 CitationsSource
#1Xiang Fang (SCUT: South China University of Technology)H-Index: 2
#2Jiangguo Lin (SCUT: South China University of Technology)H-Index: 6
Last. Jianhua WuH-Index: 11
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Force-regulated cleavage of A2 domain of von Willebrand factor (vWF) by ADAMTS13 is a key event in preventing thrombotic thrombocytopenic purpura (TTP). Recognition and cleavage depend on cooperative and modular contacts between several ADAMTS13 subdomains and discrete segments of vWF A2 domain. Spacer domain of ADAMTS13 contains an important exosite interacting with α6 helix of unfold A2 domain, but it remains unclear whether stretching of α6 regulates binding to spacer. To understand the molec...
2 CitationsSource
#1Chien-Yun Lee (TUM: Technische Universität München)H-Index: 1
#2Dongxue Wang (TUM: Technische Universität München)H-Index: 3
Last. Bernhard Kuster (TUM: Technische Universität München)H-Index: 61
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Citrullination is a posttranslational modification of arginine catalyzed by five peptidylarginine deiminases (PADs) in humans. The loss of a positive charge may cause structural or functional alterations, and while the modification has been linked to several diseases, including rheumatoid arthritis (RA) and cancer, its physiological or pathophysiological roles remain largely unclear. In part, this is owing to limitations in available methodology to robustly enrich, detect, and localize the modif...
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#1Thilo Witsch (Harvard University)H-Index: 7
#2Kimberly Martinod (Katholieke Universiteit Leuven)H-Index: 21
Last. Denisa D. Wagner (Harvard University)H-Index: 103
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BackgroundA disintegrin‐like metalloproteinase with thrombospondin motif type 1 member 13 (ADAMTS13), the von Willebrand factor–cleaving enzyme, decreases leukocyte and platelet recruitment and, th...
4 CitationsSource
#1Bogac Ercig (UM: Maastricht University)H-Index: 2
#2Kanin WichapongH-Index: 6
Last. Gerry A. F. NicolaesH-Index: 29
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ADAMTS13 (a disintegrin and metalloprotease with a thrombospondin type-1 motif, member 13) and von Willebrand factor (VWF) can be considered as scale weights which control platelet adhesion during primary haemostasis. In a very uncommon condition designated thrombotic thrombocytopenic purpura (TTP), functional absence of ADAMTS13 tips the balance toward VWF-mediated platelet adhesion in the microcirculation. TTP is associated with a high mortality and arises from either a congenital or acquired ...
3 CitationsSource
Cited By4
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#1Yvonne Döring (LMU: Ludwig Maximilian University of Munich)H-Index: 23
#2Peter Libby (Brigham and Women's Hospital)H-Index: 187
Last. Oliver Soehnlein (LMU: Ludwig Maximilian University of Munich)H-Index: 51
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Neutrophil extracellular traps (NETs) have recently emerged as a newly recognized contributor to venous and arterial thrombosis. These strands of DNA extruded by activated or dying neutrophils, decorated with various protein mediators, become solid-state reactors that can localize at the critical interface of blood with the intimal surface of diseased arteries and propagate and amplify the regional injury. NETs thus furnish a previously unsuspected link between inflammation, innate immunity, thr...
1 CitationsSource
#1Siu Ling Wong (Harvard University)H-Index: 17
#2Jeremy Goverman (Shriners Hospitals for Children)H-Index: 16
Last. Denisa D. Wagner (Harvard University)H-Index: 103
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Enhancing skin allograft longevity lessens the need for new allografts before optimal intervention is available. Reduced activity of ADAMTS13 (an enzyme that cleaves the pro-thrombotic and proinflammatory von Willebrand factor) and presence of neutrophil extracellular traps (NETs) have been implicated in liver and lung allograft failures. The effect of ADAMTS13 treatment and the impact of NETs on skin allografts, however, remain unexplored. Here, we adopted a murine model of complete mismatch fu...
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#1Shu‐Yan Yang (Shanxi Medical University)
#2Ling‐Yuan Zeng (Shanxi Medical University)
Last. Hong Yan (Shanxi Medical University)
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OBJECTIVE: To investigate the relationship between primary femoral head necrosis (ONFH) and an ABO blood group. METHODS: This study was a retrospective case-control trial. An analysis of the clinical data of an ABO blood group with 516 patients (case group) with ONFH and 489 limb-fracture patients (control group) without previous hip pain was obtained from the Second Hospital of Shanxi Medical University from November 2015 to November 2018. The clinical data included gender, age, height, weight,...
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#1Imre Varjú (Columbia University)H-Index: 1
#2Krasimir Kolev (Semmelweis University)H-Index: 10
Abstract Neutrophil extracellular traps (NETs) are DNA and histone-based networks enriched with granule-derived proteins cast out by neutrophils in response to various inflammatory stimuli. Another molecular network, fibrin is the primary protein scaffold that holds both physiological blood clots and pathological thrombi together. There is mounting evidence that NETs and fibrin form a composite network within thrombi: in the past 10 years, a variety of molecular pathways have been revealed that ...
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Systemic lupus erythematosus (SLE) is an autoimmune syndrome of unknown etiology, characterized by multi-organ inflammation and clinical heterogeneity. SLE affects mostly women and is associated with a high risk of cardiovascular disease. As the therapeutic management of SLE improved, a pattern of early atherosclerotic disease became one of the hallmarks of late disease morbidity and mortality. Neutrophils emerged as important players in SLE pathogenesis and they are associated with increased ri...
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#2Zachary T. Hilt (UR: University of Rochester)H-Index: 1
Last. Preeti Maurya (UR: University of Rochester)
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#1Clare M. Waterman (NIH: National Institutes of Health)H-Index: 32
#2Hawa Racine Thiam (NIH: National Institutes of Health)H-Index: 1
Last. Denisa D. Wagner (Boston Children's Hospital)H-Index: 103
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Neutrophil extracellular traps (NETs) are web-like DNA structures decorated with histones and cytotoxic proteins that are released by activated neutrophils to trap and neutralize pathogens during the innate immune response, but also form in and exacerbate sterile inflammation. Peptidylarginine deiminase 4 (PAD4) citrullinates histones and is required for NET formation (NETosis) in mouse neutrophils. While the in vivo impact of NETs is accumulating, the cellular events driving NETosis and the rol...
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