ArticleCirculation research2019
Plasma Peptidylarginine Deiminase IV Promotes VWF-Platelet String Formation and Accelerates Thrombosis After Vessel Injury.
Article in Circulation research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Epidemiology and Risk Factors of Portal Venous System Thrombosis in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.Frontiers in medicine · 2021Pooled it
- Review
- The regulatory role of post-translational modifications in the pathogenesis of ulcerative colitis.Molecular biology reports · 2026Review
- Mouse models to study von Willebrand factor in inflammation: a scoping review.Intensive care medicine experimental · 2026Review
- Toward improved thrombolysis in ischemic stroke: targeting nonfibrin components.Research and practice in thrombosis and haemostasis · 2026Review
- Review
- Plasmin-mediated proteolysis of von Willebrand factor in patients with acute and chronic liver disease.Research and practice in thrombosis and haemostasis · 2025Article
- Role of platelets and NETs in arterial thrombosis.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Influence of homocysteine on regulating immunothrombosis: mechanisms and therapeutic potential in management of infections.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Arginine Methylation by PRMT1 Affects ADAMTS13 Secretion and Enzymatic Activity.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Review
- Blocking peptidyl arginine deiminase 4 confers neuroprotective effect in the post-ischemic brain through both NETosis-dependent and -independent mechanisms.Acta neuropathologica communications · 2025Article
- The Role of Neutrophil Extracellular Traps in Atherosclerosis: From the Molecular to the Clinical Level.Journal of inflammation research · 2025Review
- NET burden in left atrial blood is associated with biomarkers of thrombosis and cardiac injury in patients with enlarged left atria.Clinical research in cardiology : official journal of the German Cardiac Society · 2025Article
- Pharmacological blocking of neutrophil extracellular traps attenuates immunothrombosis and neuroinflammation in cerebral cavernous malformation.Nature cardiovascular research · 2024Article
- Reflections on Targeting Neutrophil Extracellular Traps in Deep Vein Thrombosis.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Current Knowledge of Enterococcal Endocarditis: A Disease Lurking in Plain Sight of Health Providers.Pathogens (Basel, Switzerland) · 2024Review
- NETworking for Health and in Disease: Neutrophil Extracellular Traps in Pediatric Surgical Care.Children (Basel, Switzerland) · 2024Review
- Article
- Role and intervention of PAD4 in NETs in acute respiratory distress syndrome.Respiratory research · 2024Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
rationalePAD4 (peptidylarginine deiminase type IV), an enzyme essential for neutrophil extracellular trap formation (NETosis), is released together with neutrophil extracellular traps into the extracellular milieu. It citrullinates histones and holds the potential to citrullinate other protein targets. While NETosis is implicated in thrombosis, the impact of the released PAD4 is unknown.
objectiveThis study tests the hypothesis that extracellular PAD4, released during inflammatory responses, citrullinates plasma proteins, thus affecting thrombus formation. METHODS AND
resultsHere, we show that injection of r-huPAD4 in vivo induces the formation of VWF (von Willebrand factor)-platelet strings in mesenteric venules and that this is dependent on PAD4 enzymatic activity. VWF-platelet strings are naturally cleaved by ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type-1 motif-13). We detected a reduction of endogenous ADAMTS13 activity in the plasma of wild-type mice injected with r-huPAD4. Using mass spectrometry and in vitro studies, we found that r-huPAD4 citrullinates ADAMTS13 on specific arginine residues and that this modification dramatically inhibits ADAMTS13 enzymatic activity. Elevated citrullination of ADAMTS13 was observed in plasma samples of patients with sepsis or noninfected patients who were elderly (eg, age >65 years) and had underlying comorbidities (eg, diabetes mellitus and hypertension) as compared with healthy donors. This shows that ADAMTS13 is citrullinated in vivo. VWF-platelet strings that form on venules of Adamts13
conclusionsOur data indicate that PAD4 in circulation reduces VWF-platelet string clearance and accelerates the formation of a stable platelet plug after vessel injury. We propose that this effect is, at least in part, due to ADAMTS13 inhibition.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.