{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:46Z","timestamp":1787028526031,"version":"build-2736575974"},"reference-count":179,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T00:00:00Z","timestamp":1702944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Thromboinflammation, the interplay between thrombosis and inflammation, is a significant pathway that drives cardiovascular and autoimmune diseases, as well as COVID-19. SARS-CoV-2 causes inflammation and blood clotting issues. Innate immune cells have emerged as key modulators of this process. Neutrophils, the most predominant white blood cells in humans, are strategically positioned to promote thromboinflammation. By releasing decondensed chromatin structures called neutrophil extracellular traps (NETs), neutrophils can initiate an organised cell death pathway. These structures are adorned with histones, cytoplasmic and granular proteins, and have cytotoxic, immunogenic, and prothrombotic effects that can hasten disease progression. Protein arginine deiminase 4 (PAD4) catalyses the citrullination of histones and is involved in the release of extracellular DNA (NETosis). The neutrophil inflammasome is also required for this process. Understanding the link between the immunological function of neutrophils and the procoagulant and proinflammatory activities of monocytes and platelets is important in understanding thromboinflammation. This text discusses how vascular blockages occur in thromboinflammation due to the interaction between neutrophil extracellular traps and ultra-large VWF (von Willebrand Factor). The activity of PAD4 is important for understanding the processes that drive thromboinflammation by linking the immunological function of neutrophils with the procoagulant and proinflammatory activities of monocytes and platelets. This article reviews how vaso-occlusive events in thrombo-inflammation occur through the interaction of neutrophil extracellular traps with von Willebrand factor. It highlights the relevance of PAD4 in neutrophil inflammasome assembly and neutrophil extracellular traps in thrombo-inflammatory diseases such as atherosclerosis and cardiovascular disease. Interaction between platelets, VWF, NETs and inflammasomes is critical for the progression of thromboinflammation in several diseases and was recently shown to be active in COVID-19.<\/jats:p>","DOI":"10.3390\/ijms25010047","type":"journal-article","created":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T11:17:24Z","timestamp":1702984644000},"page":"47","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["To Gain Insights into the Pathophysiological Mechanisms of the Thrombo-Inflammatory Process in the Atherosclerotic Plaque"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9705-5360","authenticated-orcid":false,"given":"Francesco","family":"Nappi","sequence":"first","affiliation":[{"name":"Department of Cardiac Surgery, Centre Cardiologique du Nord, 93200 Saint-Denis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1056\/NEJM199901143400207","article-title":"Atherosclerosis\u2014An inflammatory disease","volume":"340","author":"Ross","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Nappi, F., Bellomo, F., and Avtaar Singh, S.S. (2023). Worsening Thrombotic Complication of Atherosclerotic Plaques Due to Neutrophils Extracellular Traps: A Systematic Review. Biomedicines, 11.","DOI":"10.3390\/biomedicines11010113"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Trivigno, S.M.G., Guidetti, G.F., Barbieri, S.S., and Zar\u00e0, M. (2023). Blood Platelets in Infection: The Multiple Roles of the Platelet Signalling Machinery. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24087462"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1198952","DOI":"10.3389\/fimmu.2023.1198952","article-title":"Neutrophil extracellular traps mediate deep vein thrombosis: From mechanism to therapy","volume":"14","author":"Yao","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nri3345","article-title":"Thrombosis as an intravascular effector of innate immunity","volume":"13","author":"Engelmann","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e99445","DOI":"10.1172\/jci.insight.99445","article-title":"Neutrophil accumulation and NET release contribute to thrombosis in HIT","volume":"3","author":"Gollomp","year":"2018","journal-title":"JCI Insight"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1055\/a-2113-1134","article-title":"Flow Chamber Analyses in Cardiovascular Research: Impact of Platelets and the Intercellular Crosstalk with Endothelial Cells, Leukocytes, and Red Blood Cells","volume":"43","author":"Krott","year":"2023","journal-title":"Hamostaseologie"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3378","DOI":"10.1172\/JCI27196","article-title":"Platelets in inflammation and atherogenesis","volume":"115","author":"Gawaz","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1161\/01.ATV.0000095974.95122.EC","article-title":"Platelets in inflammation and thrombosis","volume":"23","author":"Wagner","year":"2003","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1161\/CIRCULATIONAHA.123.065190","article-title":"Effect of the P-Selectin Inhibitor Crizanlizumab on Survival Free of Organ Support in Patients Hospitalized for COVID-19: A Randomized Controlled Trial","volume":"148","author":"Solomon","year":"2023","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/0092-8674(93)80055-J","article-title":"Leukocyte rolling and extravasation are severely compromised in P selectin-deficient mice","volume":"74","author":"Mayadas","year":"1993","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1038\/nm899","article-title":"Interaction of P-selectin and PSGL-1 generates microparticles that correct hemostasis in a mouse model of hemophilia A","volume":"9","author":"Cambien","year":"2003","journal-title":"Nat. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1111\/j.1538-7836.2005.01373.x","article-title":"The P-selectin, tissue factor, coagulation triad","volume":"3","author":"Polgar","year":"2005","journal-title":"J. Thromb. Haemost."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.ejphar.2008.06.102","article-title":"Primary and secondary capture of platelets onto inflamed femoral artery endothelium is dependent on P-selectin and PSGL-1","volume":"592","author":"Braun","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1160\/TH07-03-0207","article-title":"PSGL-1 regulates platelet P-selectin-mediated endothelial activation and shedding of P-selectin from activated platelets","volume":"98","author":"Dole","year":"2007","journal-title":"Thromb. Haemost."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2334","DOI":"10.1182\/blood-2005-04-1530","article-title":"Activated platelets induce Weibel-Palade-body secretion and leukocyte rolling in vivo: Role of P-selectin","volume":"106","author":"Dole","year":"2005","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1016\/j.ehj.2003.08.021","article-title":"The adhesion molecule P-selectin and cardiovascular disease","volume":"24","author":"Blann","year":"2003","journal-title":"Eur. Heart J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1161\/01.CIR.103.4.491","article-title":"Soluble P-selectin and the risk of future cardiovascular events","volume":"103","author":"Ridker","year":"2001","journal-title":"Circulation"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1161\/CIRCRESAHA.117.310795","article-title":"Circulating Platelets as Mediators of Immunity, Inflammation, and Thrombosis","volume":"122","author":"Koupenova","year":"2018","journal-title":"Circ. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6015","DOI":"10.1182\/blood-2008-10-186650","article-title":"Elevated levels of soluble P-selectin in mice alter blood-brain barrier function, exacerbate stroke, and promote atherosclerosis","volume":"113","author":"Kisucka","year":"2009","journal-title":"Blood"},{"key":"ref_21","unstructured":"NIHR Global Health Unit on Global Surgery (2022). Elective surgery system strengthening development, measurement, and validation of the surgical preparedness index across 1632 hospitals in 119 countries. COVIDSurg Collaborative. Lancet, 400, 1607\u20131617."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"COVIDSurg Collaborative, and GlobalSurg Collaborative (2022). SARS-CoV-2 infection and venous thromboembolism after surgery: An international prospective cohort study. Anaesthesia, 77, 28\u201339.","DOI":"10.1111\/anae.15563"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"COVIDSurg Collaborative, and GlobalSurg Collaborative (2021). SARS-CoV-2 vaccination modelling for safe surgery to save lives: Data from an international prospective cohort study. Br. J. Surg., 108, 1056\u20131063.","DOI":"10.1093\/bjs\/znab101"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"COVIDSurg Collaborative, and GlobalSurg Collaborative (2021). Timing of surgery following SARS-CoV-2 infection: An international prospective cohort study. Anaesthesia, 76, 748\u2013758.","DOI":"10.1111\/anae.15458"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"COVIDSurg Collaborative, and GlobalSurg Collaborative (2021). Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: An international prospective cohort study. Anaesthesia, 76, 1454\u20131464.","DOI":"10.1111\/anae.15560"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Nappi, F., Giacinto, O., Ellouze, O., Nenna, A., Avtaar Singh, S.S., Chello, M., Bouzguenda, A., and Copie, X. (2022). Association between COVID-19 Diagnosis and Coronary Artery Thrombosis: A Narrative Review. Biomedicines, 10.","DOI":"10.3390\/biomedicines10030702"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e405","DOI":"10.1016\/j.athoracsur.2020.04.008","article-title":"Acute Type A Aortic Dissection During the COVID-19 Outbreak","volume":"110","author":"Fukuhara","year":"2020","journal-title":"Ann. Thorac. Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.athoracsur.2021.02.066","article-title":"Incertitude Pathophysiology and Management During the First Phase of the COVID-19 Pandemic","volume":"113","author":"Nappi","year":"2022","journal-title":"Ann. Thorac. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"102160","DOI":"10.1016\/j.rpth.2023.102160","article-title":"New insight into the traditional model of the coagulation cascade and its regulation: Illustrated review of a three-dimensional view","volume":"7","author":"Troisi","year":"2023","journal-title":"Res Pract Thromb. Haemost."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"960398","DOI":"10.3389\/fcvm.2023.960398","article-title":"Platelet-monocyte aggregates: Molecular mediators of thromboinflammation","volume":"10","author":"Rolling","year":"2023","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1161\/ATVBAHA.117.309846","article-title":"Tissue factor: An essential mediator of hemostasis and trigger of thrombosis","volume":"38","author":"Grover","year":"2018","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Heestermans, M., Poenou, G., Duchez, A.C., Hamzeh-Cognasse, H., Bertoletti, L., and Cognasse, F. (2022). Immunothrombosis and the Role of Platelets in Venous Thromboembolic Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113176"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1055\/s-0037-1613351","article-title":"Transfer of tissue factor from platelets to monocytes: Role of platelet-derived microvesicles and CD62P","volume":"88","author":"Scholz","year":"2002","journal-title":"Thromb. Haemost."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"13397","DOI":"10.1038\/s41598-019-49635-7","article-title":"Platelet P-selectin triggers rapid surface exposure of tissue factor in monocytes","volume":"9","author":"Ivanov","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"13835","DOI":"10.1073\/pnas.250475997","article-title":"Pro-coagulant state resulting from high levels of soluble P-selectin in blood","volume":"97","author":"Hartwell","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1182\/blood-2002-07-2209","article-title":"Platelet P-selectin facilitates atherosclerotic lesion development","volume":"101","author":"Burger","year":"2003","journal-title":"Blood"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Klopf, J., Brostjan, C., Eilenberg, W., and Neumayer, C. (2021). Neutrophil Extracellular Traps and Their Implications in Cardiovascular and Inflammatory Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020559"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/nm810","article-title":"Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E","volume":"9","author":"Huo","year":"2003","journal-title":"Nat. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1161\/ATVBAHA.107.159327","article-title":"Role of smooth muscle cells in the initiation and early progression of atherosclerosis","volume":"28","author":"Doran","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1161\/ATVBAHA.118.310958","article-title":"Novel antiatherosclerotic therapies","volume":"39","author":"Libby","year":"2019","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1161\/CIRCULATIONAHA.123.063760","article-title":"INKILN is a Novel Long Noncoding RNA Promoting Vascular Smooth Muscle Inflammation via Scaffolding MKL1 and USP10","volume":"148","author":"Zhang","year":"2023","journal-title":"Circulation"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1007\/s11626-023-00808-9","article-title":"Platelet factor 4 (PF4) induces cluster of differentiation 40 (CD40) expression in human aortic endothelial cells (HAECs) through the SIRT1\/NF-\u03baB\/p65 signaling pathway","volume":"59","author":"Zhong","year":"2023","journal-title":"Vitr. Cell. Dev. Biol. Anim."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3545","DOI":"10.1182\/blood-2004-07-2617","article-title":"Endothelial expression of E-selectin is induced by the platelet-specific chemokine platelet factor 4 through LRP in an NF-kappaB-dependent manner","volume":"105","author":"Yu","year":"2005","journal-title":"Blood"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1002\/eji.201041196","article-title":"Rap1a activation by CalDAG-GEFI and p38 MAPK is involved in E-selectin-dependent slow leukocyte rolling","volume":"41","author":"Stadtmann","year":"2011","journal-title":"Eur. J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e060756","DOI":"10.1136\/bmjopen-2022-060756","article-title":"Predictive value of combining leucocyte and platelet counts for mortality in ST-segment elevation myocardial infarction patients after percutaneous coronary intervention treatment in Chinese population: A retrospective cohort study","volume":"13","author":"Yuan","year":"2023","journal-title":"BMJ Open"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1182\/blood-2012-06-437392","article-title":"Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice","volume":"121","author":"Duerschmied","year":"2013","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1182\/blood-2015-01-624023","article-title":"P-selectin promotes neutrophil extracellular trap formation in mice","volume":"126","author":"Etulain","year":"2015","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Yun, S.H., Sim, E.H., Goh, R.Y., Park, J.I., and Han, J.Y. (2016). Platelet activation: The mechanisms and potential biomarkers. Biomed Res. Int., 2016.","DOI":"10.1155\/2016\/9060143"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4958","DOI":"10.1182\/blood-2007-11-123620","article-title":"Inflammation induces hemorrhage in thrombocytopenia","volume":"111","author":"Goerge","year":"2008","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6851","DOI":"10.1158\/0008-5472.CAN-08-0718","article-title":"Platelet granule secretion continuously prevents intratumor hemorrhage","volume":"68","author":"Goerge","year":"2008","journal-title":"Cancer Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2900","DOI":"10.1038\/s41467-023-38624-0","article-title":"Platelet-derived chemokines promote skeletal muscle regeneration by guiding neutrophil recruitment to injured muscles","volume":"14","author":"Graca","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.3389\/fimmu.2019.01472","article-title":"Nox2 Regulates Platelet Activation and NET Formation in the Lung","volume":"10","author":"Hook","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1083\/jcb.200606027","article-title":"Novel cell death program leads to neutrophil extracellular traps","volume":"176","author":"Fuchs","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5271","DOI":"10.1182\/blood-2008-01-078204","article-title":"The vessel wall and its interactions","volume":"111","author":"Wagner","year":"2008","journal-title":"Blood"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Nappi, F., Nappi, P., Gambardella, I., and Avtaar Singh, S.S. (2022). Thromboembolic Disease and Cardiac Thrombotic Complication in COVID-19: A Systematic Review. Metabolites, 12.","DOI":"10.3390\/metabo12100889"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1146\/annurev-cellbio-020520-111016","article-title":"Cellular mechanisms of NETosis","volume":"36","author":"Thiam","year":"2020","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Nappi, F., Bellomo, F., and Avtaar Singh, S.S. (2022). Insights into the Role of Neutrophils and Neutrophil Extracellular Traps in Causing Cardiovascular Complications in Patients with COVID-19: A Systematic Review. J. Clin. Med., 11.","DOI":"10.3390\/jcm11092460"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Nappi, F., Iervolino, A., and Avtaar Singh, S.S. (2021). Thromboembolic Complications of SARS-CoV-2 and Metabolic Derangements: Suggestions from Clinical Practice Evidence to Causative Agents. Metabolites, 11.","DOI":"10.3390\/metabo11060341"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"fj201800691R","DOI":"10.1096\/fj.201800691R","article-title":"Peptidylarginine deiminase 4: A nuclear button triggering neutrophil extracellular traps in inflammatory diseases and aging","volume":"32","author":"Wong","year":"2018","journal-title":"FASEB J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"683803","DOI":"10.3389\/fimmu.2021.683803","article-title":"NLRP3 inflammasome assembly in neutrophils is supported by PAD4 and promotes NETosis under Sterile Conditions","volume":"12","author":"Negro","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/nm.3887","article-title":"Diabetes primes neutrophils to undergo NETosis, which impairs wound healing","volume":"21","author":"Wong","year":"2015","journal-title":"Nat. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"22655","DOI":"10.1073\/pnas.2015951117","article-title":"Reply to Liu: The disassembly of the actin cytoskeleton is an early event during NETosis","volume":"117","author":"Thiam","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1161\/CIRCRESAHA.119.314581","article-title":"Extracellular DNA NET-works with dire consequences for health","volume":"125","author":"Sorvillo","year":"2019","journal-title":"Circ. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"eaar6689","DOI":"10.1126\/sciimmunol.aar6689","article-title":"Gasdermin D plays a vital role in the generation of neutrophil extracellular traps","volume":"3","author":"Sollberger","year":"2018","journal-title":"Sci. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"eaao4747","DOI":"10.1126\/sciimmunol.aao4747","article-title":"National Heart, Lung, and Blood Institute Severe Asthma Research Program-3 Investigators. Neutrophil cytoplasts induce TH17 differentiation and skew inflammation toward neutrophilia in severe asthma","volume":"3","author":"Krishnamoorthy","year":"2018","journal-title":"Sci. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2784","DOI":"10.1182\/blood-2013-04-457671","article-title":"NETosis: How vital is it?","volume":"122","author":"Yipp","year":"2013","journal-title":"Blood"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1002\/art.42093","article-title":"The prominent role of hematopoietic peptidyl arginine deiminase 4 in arthritis: Collagen- and granulocyte colony-stimulating factor-induced arthritis model in C57BL\/6 MICE","volume":"74","author":"Fukui","year":"2022","journal-title":"Arthritis Rheumatol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1161\/CIRCRESAHA.119.315601","article-title":"PAD4 and von Willebrand Factor Link Inflammation and Thrombosis","volume":"125","author":"Morrell","year":"2019","journal-title":"Circ. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1161\/CIRCRESAHA.118.314571","article-title":"Plasma peptidylarginine deiminase IV promotes VWF-platelet string formation and accelerates thrombosis after vessel injury","volume":"125","author":"Sorvillo","year":"2019","journal-title":"Circ. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/ni.2913","article-title":"The adaptor ASC has extracellular and \u2018prionoid\u2019 activities that propagate inflammation","volume":"15","author":"Franklin","year":"2014","journal-title":"Nat. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Liberale, L., Holy, E.W., Akhmedov, A., Bonetti, N.R., Nietlispach, F., Matter, C.M., Mach, F., Montecucco, F., Beer, J.H., and Paneni, F. (2019). Interleukin-1\u03b2 mediates arterial thrombus formation via NET-associated tissue factor. J. Clin. Med., 8.","DOI":"10.3390\/jcm8122072"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1177\/0333102414529671","article-title":"Circulating endothelial microparticles in female migraineurs with aura","volume":"35","author":"Liman","year":"2015","journal-title":"Cephalalgia"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"641750","DOI":"10.3389\/fimmu.2021.641750","article-title":"Inflammasome-dependent coagulation activation in sepsis","volume":"12","author":"Wu","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1182\/blood-2013-10-463646","article-title":"Thrombosis: Tangled up in NETs","volume":"123","author":"Martinod","year":"2014","journal-title":"Blood"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1161\/CIRCRESAHA.120.315931","article-title":"Neutrophil extracellular traps participate in cardiovascular diseases: Recent experimental and clinical insights","volume":"126","author":"Libby","year":"2020","journal-title":"Circ. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41577-021-00536-9","article-title":"Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19","volume":"21","author":"Bonaventura","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1001\/jamacardio.2020.3551","article-title":"Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases","volume":"5","author":"Lindner","year":"2020","journal-title":"JAMA Cardiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e2346","DOI":"10.1212\/WNL.0000000000009532","article-title":"Thrombus NET content is associated with clinical outcome in stroke and myocardial infarction","volume":"94","author":"Novotny","year":"2020","journal-title":"Neurology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1161\/STROKEAHA.117.019896","article-title":"Thrombus neutrophil extracellular traps content impair tPA-induced thrombolysis in acute ischemic stroke","volume":"49","author":"Ducroux","year":"2018","journal-title":"Stroke"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1001\/jamacardio.2020.7308","article-title":"Assessment of Neutrophil Extracellular Traps in Coronary Thrombus of a Case Series of Patients With COVID-19 and Myocardial Infarction","volume":"6","author":"Blasco","year":"2021","journal-title":"JAMA Cardiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.recesp.2016.06.006","article-title":"Immunohistological analysis of intracoronary thrombus aspirate in STEMI patients: Clinical implications of pathological findings","volume":"70","author":"Blasco","year":"2017","journal-title":"Rev. Esp. Cardiol. (Engl. Ed.)"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5007","DOI":"10.1038\/s41598-020-61971-7","article-title":"Double-Stranded DNA and NETs Components in Relation to Clinical Outcome After ST-Elevation Myocardial Infarction","volume":"10","author":"Langseth","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"610696","DOI":"10.3389\/fimmu.2020.610696","article-title":"Insights into immunothrombosis: The interplay among neutrophil extracellular trap, von Willebrand Factor, and ADAMTS13","volume":"11","author":"Yang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1146\/annurev-med-061813-013241","article-title":"ADAMTS13 and von Willebrand factor in thrombotic thrombocytopenic purpura","volume":"66","author":"Zheng","year":"2015","journal-title":"Annu. Rev. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1182\/blood-2018-02-769000","article-title":"Inflammation, von Willebrand factor, and ADAMTS13","volume":"132","author":"Chen","year":"2018","journal-title":"Blood"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3452","DOI":"10.1182\/blood-2007-08-108571","article-title":"The combined roles of ADAMTS13 and VWF in murine models of TTP, endotoxemia, and thrombosis","volume":"111","author":"Chauhan","year":"2008","journal-title":"Blood"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1182\/blood-2017-04-636431","article-title":"Pathophysiology of thrombotic thrombocytopenic purpura","volume":"130","author":"Sadler","year":"2017","journal-title":"Blood"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1172\/JCI30920","article-title":"Sickle cell disease: Old discoveries, new concepts, and future promise","volume":"117","author":"Frenette","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3818","DOI":"10.1182\/blood-2013-10-529982","article-title":"Heme-induced neutrophil extracellular traps contribute to the pathogenesis of sickle cell disease","volume":"123","author":"Chen","year":"2014","journal-title":"Blood"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1182\/blood-2014-05-378638","article-title":"von Willebrand factor, Jedi knight of the bloodstream","volume":"124","author":"Springer","year":"2014","journal-title":"Blood"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3971","DOI":"10.1182\/blood-2001-11-0060","article-title":"Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein Ib-IX complex: Studies using optical tweezers","volume":"99","author":"Arya","year":"2002","journal-title":"Blood"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1111\/jth.14686","article-title":"Von Willebrand factor and ADAMTS13 impact on the outcome of Staphylococcus aureus sepsis","volume":"18","author":"Peetermans","year":"2020","journal-title":"J. Thromb. Haemost."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1111\/j.1538-7836.2006.01949.x","article-title":"von Willebrand factor, endothelial dysfunction, and cardiovascular disease","volume":"4","author":"Vischer","year":"2006","journal-title":"J. Thromb. Haemost."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/j.1538-7836.2010.04134.x","article-title":"Plasma levels of von Willebrand factor in the etiologic subtypes of ischemic stroke","volume":"9","author":"Hanson","year":"2011","journal-title":"J. Thromb. Haemost."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1084\/jem.20080130","article-title":"ADAMTS13: A new link between thrombosis and inflammation","volume":"205","author":"Chauhan","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"5224","DOI":"10.1182\/blood-2012-06-440255","article-title":"ADAMTS13 deficiency exacerbates VWF-dependent acute myocardial ischemia\/reperfusion injury in mice","volume":"120","author":"Gandhi","year":"2012","journal-title":"Blood"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"5217","DOI":"10.1182\/blood-2012-06-439935","article-title":"Protective anti-inflammatory effect of ADAMTS13 on myocardial ischemia\/reperfusion injury in mice","volume":"120","author":"Savchenko","year":"2012","journal-title":"Blood"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3329","DOI":"10.1182\/blood-2009-03-213264","article-title":"von Willebrand factor-cleaving protease ADAMTS13 reduces ischemic brain injury in experimental stroke","volume":"114","author":"Zhao","year":"2009","journal-title":"Blood"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2274","DOI":"10.1111\/jth.13493","article-title":"Histones link inflammation and thrombosis through the induction of Weibel-Palade body exocytosis","volume":"14","author":"Michels","year":"2016","journal-title":"J. Thromb. Haemost."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/j.toxicon.2005.02.023","article-title":"Structure and function of snake venom toxins interacting with human von Willebrand factor","volume":"45","author":"Matsui","year":"2005","journal-title":"Toxicon"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"100116","DOI":"10.1016\/j.rpth.2023.100116","article-title":"Novel mechanisms of thrombo-inflammation during infection: Spotlight on neutrophil extracellular trap-mediated platelet activation","volume":"7","author":"Colicchia","year":"2023","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e12782","DOI":"10.1111\/micc.12782","article-title":"Histone-stimulated platelet adhesion to mouse cremaster venules in vivo is dependent on von Willebrand factor","volume":"29","author":"Courson","year":"2022","journal-title":"Microcirculation"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0049-3848(97)00096-0","article-title":"Binding of the von Willebrand factor A1 domain to histone","volume":"86","author":"Ward","year":"1997","journal-title":"Thromb. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1111\/jth.15873","article-title":"Mechanisms of ADAMTS13 regulation","volume":"20","author":"DeYoung","year":"2022","journal-title":"J. Thromb. Haemost."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1111\/ajt.15703","article-title":"Recombinant human ADAMTS13 treatment and anti-NET strategies enhance skin allograft survival in mice","volume":"20","author":"Wong","year":"2020","journal-title":"Am. J. Transplant."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3189","DOI":"10.1038\/s41598-023-30246-2","article-title":"Alleviation of arthritis through prevention of neutrophil extracellular traps by an orally available inhibitor of protein arginine deiminase 4","volume":"13","author":"Gajendran","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"3979","DOI":"10.1182\/bloodadvances.2021006405","article-title":"Interaction of von Willebrand factor with blood cells in flow models: A systematic review","volume":"6","author":"Arisz","year":"2022","journal-title":"Blood Adv."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/0014-5793(89)81376-6","article-title":"Sleath Activation of interleukin-1 beta by a co-induced protease","volume":"247","author":"Black","year":"1989","journal-title":"PR. FEBS Lett."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"5323","DOI":"10.1016\/S0021-9258(18)83546-3","article-title":"A pre-aspartate-specific protease from human leukocytes that cleaves pro-interleukin-1 beta","volume":"264","author":"Black","year":"1989","journal-title":"J. Biol. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"8376","DOI":"10.1016\/S0021-9258(18)92986-8","article-title":"Purification and characterization of a novel thiol protease involved in processing the enkephalin precursor","volume":"266","author":"Krieger","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/ni.1703","article-title":"The inflammasome: A caspase-1-activation platform that regulates immune responses and disease pathogenesis","volume":"10","author":"Franchi","year":"2009","journal-title":"Nat. Immunol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e20190314","DOI":"10.1084\/jem.20190314","article-title":"Inflammasome signaling and regulation of interleukin-1 family cytokines","volume":"217","author":"Chan","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Libby, P. (2021). Targeting inflammatory pathways in cardiovascular disease: The inflammasome, Interleukin-1, Interleukin-6 and BEYOND. Cells, 10.","DOI":"10.3390\/cells10040951"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"e169855","DOI":"10.1172\/jci.insight.169855","article-title":"Platelets exacerbate cardiovascular inflammation in a murine model of Kawasaki disease vasculitis","volume":"8","author":"Lee","year":"2023","journal-title":"JCI Insight"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"107615","DOI":"10.1016\/j.celrep.2020.107615","article-title":"Platelets fuel the inflammasome activation of innate immune cells","volume":"31","author":"Rolfes","year":"2020","journal-title":"Cell Rep."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/imr.12296","article-title":"Regulation of inflammasome activation","volume":"265","author":"Man","year":"2015","journal-title":"Immunol. Rev."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/s41421-020-0167-x","article-title":"Inflammasome activation and regulation: Toward a better understanding of complex mechanisms","volume":"6","author":"Zheng","year":"2020","journal-title":"Cell Discov."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1161\/CIRCRESAHA.118.311362","article-title":"NLRP3 Inflammasome and the IL-1 pathway in Atherosclerosis","volume":"122","author":"Grebe","year":"2018","journal-title":"Circ. Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1093\/cvr\/28.12.1808","article-title":"Enhanced leucocyte adhesion to interleukin-1 beta stimulated vascular smooth muscle cells is mainly through intercellular adhesion molecule-1","volume":"28","author":"Wang","year":"1994","journal-title":"Cardiovasc. Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/0021-9150(94)05503-B","article-title":"Interleukin-1 beta induces expression of adhesion molecules in human vascular smooth muscle cells and enhances adhesion of leukocytes to smooth muscle cells","volume":"115","author":"Wang","year":"1995","journal-title":"Atherosclerosis"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1058488","DOI":"10.3389\/fphar.2023.1058488","article-title":"Regulation by Nrf2 of IL-1\u03b2-induced inflammatory and oxidative response in VSMC and its relationship with TLR4","volume":"14","author":"Hernanz","year":"2023","journal-title":"Front. Pharmacol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"e20201466","DOI":"10.1084\/jem.20201466","article-title":"Neutrophil-specific gain- of-function mutations in Nlrp3 promote development of cryopyrin- associated periodic syndrome","volume":"218","author":"Stackowicz","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Wu, K.K., Cheung, S.W., and Cheng, K.K. (2020). NLRP3 Inflammasome Activation in Adipose Tissues and Its Implications on Metabolic Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21114184"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"795","DOI":"10.4049\/jimmunol.1800720","article-title":"Cutting edge: Protein arginine deiminase 2 and 4 regulate NLRP3 inflammasome-dependent IL-1\u03b2 maturation and ASC speck formation in macrophages","volume":"203","author":"Mishra","year":"2019","journal-title":"J. Immunol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1111\/jth.15179","article-title":"Vascular neutrophilic inflammation and immunothrombosis distinguish severe COVID-19 from influenza pneumonia","volume":"19","author":"Nicolai","year":"2021","journal-title":"J. Thromb. Haemost."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/s41573-021-00198-1","article-title":"Targeting inflammation in atherosclerosis\u2014From experimental insights to the clinic","volume":"20","author":"Soehnlein","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/s41586-021-03392-8","article-title":"The changing landscape of atherosclerosis","volume":"592","author":"Libby","year":"2021","journal-title":"Nature"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3389\/fimmu.2015.00098","article-title":"Platelets in inflammation and atherogenesis","volume":"6","author":"Nording","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1160\/TH11-08-0592","article-title":"Platelets in atherosclerosis","volume":"106","author":"Lievens","year":"2011","journal-title":"Thromb. Haemost."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.ehj.2004.01.023","article-title":"The adhesion molecule P-selectin and cardiovascular disease--cardiac surgical implications","volume":"25","author":"Koh","year":"2004","journal-title":"Eur. Heart J."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1161\/ATVBAHA.122.317162","article-title":"Thromboinflammation: From Atherosclerosis to COVID-19","volume":"42","author":"Wagner","year":"2022","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"69","DOI":"10.2174\/187152807780077345","article-title":"Therapeutic targeting of p-selectin in atherosclerosis","volume":"6","author":"Woollard","year":"2007","journal-title":"Inflamm. Allergy Drug Targets"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"e002765","DOI":"10.1161\/CIRCIMAGING.114.002765","article-title":"Molecular Imaging of Platelet-Endothelial Interactions and Endothelial von Willebrand Factor in Early and Mid-Stage Atherosclerosis","volume":"8","author":"Shim","year":"2015","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1182\/blood.V98.5.1424","article-title":"Localized reduction of atherosclerosis in von Willebrand factor-deficient mice","volume":"98","author":"Methia","year":"2001","journal-title":"Blood"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1161\/ATVBAHA.120.314459","article-title":"Differential Roles of Endothelial Cell-Derived and Smooth Muscle Cell-Derived Fibronectin Containing Extra Domain A in Early and Late Atherosclerosis","volume":"40","author":"Doddapattar","year":"2020","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1182\/blood-2011-09-376202","article-title":"ADAMTS13 reduces vascular inflammation and the development of early atherosclerosis in mice","volume":"119","author":"Gandhi","year":"2012","journal-title":"Blood"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1161\/ATVBAHA.112.247262","article-title":"Genetic ablation of Adamts13 gene dramatically accelerates the formation of early atherosclerosis in a murine model","volume":"32","author":"Jin","year":"2012","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1161\/CIRCRESAHA.117.312494","article-title":"Roles of PAD4 and NETosis in experimental atherosclerosis and arterial injury: Implications for superficial erosion","volume":"123","author":"Franck","year":"2018","journal-title":"Circ. Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41586-019-1167-6","article-title":"Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death","volume":"569","author":"Braster","year":"2019","journal-title":"Nature"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1001\/jama.2015.3130","article-title":"Hospitalization for pneumonia and risk of cardiovascular disease","volume":"313","author":"Violi","year":"2015","journal-title":"JAMA"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1161\/CIRCULATIONAHA.113.006699","article-title":"Risk for myocardial infarction and stroke after community-acquired bacteremia: A 20-year population-based cohort study","volume":"129","author":"Nielsen","year":"2014","journal-title":"Circulation"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1161\/ATVBAHA.112.300432","article-title":"Genetic and pharmacologic disruption of interleukin-1\u03b2 signaling inhibits experimental aortic aneurysm formation","volume":"33","author":"Johnston","year":"2013","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1200341","DOI":"10.3389\/fcvm.2023.1200341","article-title":"Molecular and cellular mechanisms of inflammation in atherosclerosis","volume":"10","author":"Ferdoschi","year":"2023","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1161\/CIRCULATIONAHA.117.032636","article-title":"Cholesterol Efflux Pathways Suppress Inflammasome Activation, NETosis, and Atherogenesis","volume":"138","author":"Westerterp","year":"2018","journal-title":"Circulation"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Nappi, F., and Avtaar Singh, S.S. (2022). Endothelial Dysfunction in SARS-CoV-2 Infection. Biomedicines, 10.","DOI":"10.20944\/preprints202202.0187.v1"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Nappi, F., and Avtaar Singh, S.S. (2023). Distinctive Signs of Disease as Deterrents for the Endothelial Function: A Systematic Review. Metabolites, 13.","DOI":"10.20944\/preprints202301.0392.v1"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/s41586-022-05522-2","article-title":"The WHO estimates of excess mortality associated with the COVID-19 pandemic","volume":"613","author":"Msemburi","year":"2023","journal-title":"Nature"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"315","DOI":"10.31083\/j.rcm.2020.03.126","article-title":"Endothelial dysfunction contributes to COVID-19-associated vascular inflammation and coagulopathy","volume":"21","author":"Zhang","year":"2020","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/ijlh.13500","article-title":"COVID-19: Thrombosis, thromboinflammation, and anticoagulation considerations","volume":"43","author":"Levy","year":"2021","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1161\/CIRCULATIONAHA.120.048488","article-title":"Immunothrombotic Dysregulation in COVID-19 Pneumonia Is Associated With Respiratory Failure and Coagulopathy","volume":"142","author":"Nicolai","year":"2020","journal-title":"Circulation"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0140-6736(21)01825-0","article-title":"Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial","volume":"399","author":"Group","year":"2022","journal-title":"Lancet"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Investigators R-CWCftR-C, Bradbury, C.A., Lawler, P.R., Stanworth, S.J., McVerry, B.J., McQuilten, Z., Higgins, A.M., Mouncey, S.J., Al-Beidh, F., and Rowan, K.M. (2022). Effect of antiplatelet therapy on survival and organ support-free days in critically ill patients with COVID-19: A randomized clinical trial. JAMA, 327, 1247\u20131259.","DOI":"10.1001\/jama.2022.2910"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"e630","DOI":"10.1016\/S2352-3026(20)30218-0","article-title":"Coagulation disorder in COVID-19","volume":"7","author":"Kander","year":"2020","journal-title":"Lancet Haematol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1055\/s-0041-1740182","article-title":"Associations between the von Willebrand Factor-ADAMTS13 Axis, Complement Activation, and COVID-19 Severity and Mortality","volume":"122","author":"Sinkovits","year":"2022","journal-title":"Thromb. Haemost."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"102560","DOI":"10.1016\/j.jaut.2020.102560","article-title":"Complement activation and endothelial perturbation parallel COVID-19 severity and activity","volume":"116","author":"Cugno","year":"2021","journal-title":"J. Autoimmun."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.thromres.2021.02.008","article-title":"ADAMTS 13 deficiency is associated with abnormal distribution of von Willebrand factor multimers in patients with COVID-19","volume":"204","author":"Pascreau","year":"2021","journal-title":"Thromb. Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/s41577-021-00665-1","article-title":"The state of complement in COVID-19","volume":"22","author":"Afzali","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"The Lancet Haematology (2020). COVID-19 coagulopathy: An evolving story. Lancet Haematol., 7, e425.","DOI":"10.1016\/S2352-3026(20)30151-4"},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Comer, S.P., Cullivan, S., Szklanna, P.B., Weiss, L., Cullen, S., Kelliher, S., Smolenski, A., Murphy, C., Altaie, H., and Curran, J. (2021). COVID-19 induces a hyperactive phenotype in circulating platelets. PLoS Biol., 19.","DOI":"10.1371\/journal.pbio.3001109"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s13613-021-00899-1","article-title":"Platelet activation in critically ill COVID-19 patients","volume":"11","author":"Yatim","year":"2021","journal-title":"Ann. Intensive Care."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/j.jacbts.2021.10.013","article-title":"Crizanlizumab: A CRITICAL Drug During a CRITICAL Time?","volume":"6","author":"Gue","year":"2021","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"e20200652","DOI":"10.1084\/jem.20200652","article-title":"Targeting potential drivers of COVID-19: Neutrophil extracellular traps","volume":"217","author":"Barnes","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1172\/JCI61303","article-title":"Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury","volume":"122","author":"Caudrillier","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"6335","DOI":"10.1182\/blood-2012-01-405183","article-title":"Extracellular DNA traps are associated with the pathogenesis of TRALI in humans and mice","volume":"119","author":"Thomas","year":"2012","journal-title":"Blood"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"e20201012","DOI":"10.1084\/jem.20201012","article-title":"Neutrophil extracellular traps infiltrate the lung airway, interstitial, and vascular compartments in severe COVID-19","volume":"217","author":"Radermecker","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1182\/bloodadvances.2021005949","article-title":"Inflammasome activation in neutrophils of patients with severe COVID-19","volume":"6","author":"Aymonnier","year":"2022","journal-title":"Blood Adv."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1172\/JCI9896","article-title":"Persistence of platelet thrombus formation in arterioles of mice lacking both von Willebrand factor and fibrinogen","volume":"106","author":"Ni","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1111\/j.1538-7836.2011.04422.x","article-title":"Extracellular histones increase plasma thrombin generation by impairing thrombomodulin-dependent protein C activation","volume":"9","author":"Ammollo","year":"2011","journal-title":"J. Thromb. Haemost."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1182\/blood-2010-05-287623","article-title":"von Willebrand factor-mediated platelet adhesion is critical for deep vein thrombosis in mouse models","volume":"117","author":"Brill","year":"2011","journal-title":"Blood"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1084\/jem.20112322","article-title":"Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo","volume":"209","author":"Stark","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1681\/ASN.2011111077","article-title":"Histones from dying renal cells aggravate kidney injury via TLR2 and TLR4","volume":"23","author":"Allam","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.4049\/jimmunol.1003930","article-title":"Extracellular histones are mediators of death through TLR2 and TLR4 in mouse fatal liver injury","volume":"187","author":"Xu","year":"2011","journal-title":"J. Immunol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"e12709","DOI":"10.1002\/rth2.12709","article-title":"Platelet-leukocyte interactions in COVID-19: Contributions to hypercoagulability, inflammation, and disease severity","volume":"6","author":"Hottz","year":"2022","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.cca.2019.10.033","article-title":"Citrullination of fibrinogen by peptidylarginine deiminase 2 impairs fibrin clot structure","volume":"501","author":"Damiana","year":"2020","journal-title":"Clinica Chimica Acta"},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Osca-Verdegal, R., Beltr\u00e1n-Garc\u00eda, J., Paes, A.B., Nacher-Sendra, E., Novella, S., Hermenegildo, C., Carbonell, N., Garc\u00eda-Gim\u00e9nez, J.L., and Pallard\u00f3, F.V. (2022). Histone Citrullination Mediates a Protective Role in Endothelium and Modulates Inflammation. Cells, 11.","DOI":"10.3390\/cells11244070"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"e396","DOI":"10.1161\/ATVBAHA.123.319522","article-title":"PAD4-Induced NETosis Via Cathepsin G-Mediated Platelet-Neutrophil Interaction in ChAdOx1 Vaccine-Induced Thrombosis-Brief Report","volume":"43","author":"Carnevale","year":"2023","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.1016\/j.immuni.2023.11.002","article-title":"The tumor-derived cytokine Chi3l1 induces neutrophil extracellular traps that promote T cell exclusion in triple-negative breast cancer","volume":"56","author":"Taifour","year":"2023","journal-title":"Immunity"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"00583","DOI":"10.1183\/23120541.00583-2020","article-title":"CXCL-8-dependent and -independent neutrophil activation in COPD: Experiences from a pilot study of the CXCR2 antagonist danirixin","volume":"6","author":"Keir","year":"2020","journal-title":"ERJ Open Res."},{"key":"ref_179","unstructured":"(2023, December 15). Dundee, United Kingdom, DD1 9SY GSK Investigational Site Randomized Study Evaluating the Effect of Danirixin on Neutrophil Extracellular Traps (NETs) in Chronic Obstructive Pulmonary Disease (COPD), Available online: https:\/\/www.clinicaltrials.gov\/study\/NCT03250689."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/1\/47\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:41:43Z","timestamp":1760132503000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/1\/47"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,19]]},"references-count":179,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["ijms25010047"],"URL":"https:\/\/doi.org\/10.3390\/ijms25010047","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,19]]}}}