{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:57:55Z","timestamp":1791899875076,"version":"4.3.4"},"reference-count":102,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T00:00:00Z","timestamp":1603238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["16-15-10098-P"],"award-info":[{"award-number":["16-15-10098-P"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The von Willebrand factor (vWF) is a plasma protein that mediates platelet adhesion and leukocyte recruitment to vascular injury sites and carries coagulation factor VIII, a building block of the intrinsic pathway of coagulation. The presence of ultra-large multimers of vWF in the bloodstream is associated with spontaneous thrombosis, whereas its deficiency leads to bleeding. In cardiovascular pathology, the progression of the heart valve disease results in vWF deficiency and cryptogenic gastrointestinal bleeding. The association between higher plasma levels of vWF and thrombotic complications of coronary artery disease was described. Of note, it is not the plasma levels that are crucial for vWF hemostatic activity, but vWF activation, triggered by a rise in shear rates. vWF becomes highly reactive with platelets upon unfolding into a stretched conformation, at shear rates above the critical value (more than 5000 s\u22121), which might occur at sites of arterial stenosis and injury. The activation of vWF and its counterbalance by ADAMTS-13, the vWF-cleaving protease, might contribute to complications of cardiovascular diseases. In this review, we discuss vWF involvement in complications of cardiovascular diseases and possible diagnostic and treatment approaches.<\/jats:p>","DOI":"10.3390\/ijms21207804","type":"journal-article","created":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T10:14:22Z","timestamp":1603275262000},"page":"7804","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Shear Stress-Induced Activation of von Willebrand Factor and Cardiovascular Pathology"],"prefix":"10.3390","volume":"21","author":[{"given":"Sergey","family":"Okhota","sequence":"first","affiliation":[{"name":"National Medical Research Centre of Cardiology of the Ministry of Health of the Russian Federation, 15A, 3-rd Cherepkovskaya Street, 121552 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5241-3091","authenticated-orcid":false,"given":"Ivan","family":"Melnikov","sequence":"additional","affiliation":[{"name":"National Medical Research Centre of Cardiology of the Ministry of Health of the Russian Federation, 15A, 3-rd Cherepkovskaya Street, 121552 Moscow, Russia"},{"name":"State Research Center of the Russian Federation\u2014Institute of Biomedical Problems of Russian Academy of Sciences, 76A, Khoroshevskoye Shosse, 123007 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3701-9747","authenticated-orcid":false,"given":"Yuliya","family":"Avtaeva","sequence":"additional","affiliation":[{"name":"National Medical Research Centre of Cardiology of the Ministry of Health of the Russian Federation, 15A, 3-rd Cherepkovskaya Street, 121552 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8800-1670","authenticated-orcid":false,"given":"Sergey","family":"Kozlov","sequence":"additional","affiliation":[{"name":"National Medical Research Centre of Cardiology of the Ministry of Health of the Russian Federation, 15A, 3-rd Cherepkovskaya Street, 121552 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zufar","family":"Gabbasov","sequence":"additional","affiliation":[{"name":"National Medical Research Centre of Cardiology of the Ministry of Health of the Russian Federation, 15A, 3-rd Cherepkovskaya Street, 121552 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1365-2516.2009.02005.x","article-title":"Factor VIII and von Willebrand factor interaction: Biological, clinical and therapeutic importance","volume":"16","author":"Terraube","year":"2010","journal-title":"Haemophilia"},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1111\/jth.13696","article-title":"von Willebrand factor and inflammation","volume":"15","author":"Kawecki","year":"2017","journal-title":"J. Thromb. Haemost."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3746","DOI":"10.1182\/blood-2006-03-010322","article-title":"P-selectin glycoprotein ligand 1 and \u03b22-integrins cooperate in the adhesion of leukocytes to von Willebrand factor","volume":"108","author":"Pendu","year":"2006","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Fan, M., Wang, X., Peng, X., Feng, S., Zhao, J., Liao, L., Zhang, Y., Hou, Y., and Liu, J. (2020). Prognostic value of plasma von Willebrand factor levels in major adverse cardiovascular events: A systematic review and meta-analysis. BMC Cardiovasc. Disord., 20.","DOI":"10.1186\/s12872-020-01375-7"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.atherosclerosis.2019.09.003","article-title":"Von Willebrand factor antigen levels predict major adverse cardiovascular events in patients with carotid stenosis of the ICARAS study","volume":"290","author":"Kovacevic","year":"2019","journal-title":"Atherosclerosis"},{"key":"ref_7","first-page":"207","article-title":"Current advances in circulating inflammatory biomarkers in atherosclerosis and related cardio-cerebrovascular diseases","volume":"3","author":"Lv","year":"2017","journal-title":"Chronic Dis. Transl. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/j.jacc.2018.12.045","article-title":"von Willebrand Factor and Management of Heart Valve Disease","volume":"73","author":"Vincent","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1055\/s-2006-947866","article-title":"Laboratory Testing for von Willebrand Disease: Contribution of Multimer Analysis to Diagnosis and Classification","volume":"32","author":"Budde","year":"2006","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1097\/MBC.0000000000000065","article-title":"Update on von Willebrand factor multimers: Focus on high-molecular-weight multimers and their role in hemostasis","volume":"25","author":"Stockschlaeder","year":"2014","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9226","DOI":"10.1073\/pnas.0903679106","article-title":"Structural specializations of A2, a force-sensing domain in the ultralarge vascular protein von Willebrand factor","volume":"106","author":"Zhang","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1146\/annurev.biochem.67.1.395","article-title":"Biochemistry and Genetics of von willebrand factor","volume":"67","author":"Sadler","year":"1998","journal-title":"Annu. Rev. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2884","DOI":"10.3389\/fimmu.2019.02884","article-title":"von Willebrand Factor and Platelet Glycoprotein Ib: A Thromboinflammatory Axis in Stroke","volume":"10","author":"Denorme","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7899","DOI":"10.1073\/pnas.0608422104","article-title":"Shear-induced unfolding triggers adhesion of von Willebrand factor fibers","volume":"104","author":"Schneider","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3212","DOI":"10.1182\/blood-2011-02-306597","article-title":"Unraveling the scissile bond: How ADAMTS13 recognizes and cleaves von Willebrand factor","volume":"118","author":"Crawley","year":"2011","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"L35","DOI":"10.1016\/j.bpj.2010.01.032","article-title":"Elongational Flow Induces the Unfolding of von Willebrand Factor at Physiological Flow Rates","volume":"98","author":"Sing","year":"2010","journal-title":"Biophys. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1073\/pnas.1209905110","article-title":"Atherosclerotic geometries exacerbate pathological thrombus formation poststenosis in a von Willebrand factor-dependent manner","volume":"110","author":"Westein","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7858","DOI":"10.1038\/ncomms8858","article-title":"Flow-driven assembly of VWF fibres and webs in in vitro microvessels","volume":"6","author":"Zheng","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1182\/bloodadvances.2018030122","article-title":"von Willebrand factor self-association is regulated by the shear-dependent unfolding of the A2 domain","volume":"3","author":"Zhang","year":"2019","journal-title":"Blood Adv."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1111\/j.1538-7836.2012.04797.x","article-title":"Contribution of platelet vs. endothelial VWF to platelet adhesion and hemostasis: Hemostatic effect of platelet VWF in murine VWD","volume":"10","author":"Kanaji","year":"2012","journal-title":"J. Thromb. Haemost."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1182\/blood-2015-03-632901","article-title":"Platelet-derived VWF is not essential for normal thrombosis and hemostasis but fosters ischemic stroke injury in mice","volume":"126","author":"Verhenne","year":"2015","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1182\/blood.V98.6.1662","article-title":"Purification of human von Willebrand factor\u2013cleaving protease and its identification as a new member of the metalloproteinase family","volume":"98","author":"Fujikawa","year":"2001","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1182\/blood-2005-01-0152","article-title":"Localization of ADAMTS13 to the stellate cells of human liver","volume":"106","author":"Uemura","year":"2005","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1365-2141.2004.05009.x","article-title":"Plasma levels of von Willebrand factor regulate ADAMTS-13, its major cleaving protease","volume":"126","author":"Mannucci","year":"2004","journal-title":"Br. J. Haematol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11602","DOI":"10.1073\/pnas.1018559108","article-title":"Mechanism of von Willebrand factor scissile bond cleavage by a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13)","volume":"108","author":"Xiang","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5620314","DOI":"10.1155\/2017\/5620314","article-title":"The Role of von Willebrand Factor in Vascular Inflammation: From Pathogenesis to Targeted Therapy","volume":"2017","author":"Gragnano","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4712","DOI":"10.1182\/blood-2010-03-276311","article-title":"von Willebrand factor promotes leukocyte extravasation","volume":"116","author":"Petri","year":"2010","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/jid.2013.292","article-title":"Blocking von Willebrand Factor for Treatment of Cutaneous Inflammation","volume":"134","author":"Hillgruber","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1161\/ATVBAHA.117.309319","article-title":"A Novel Single-Domain Antibody against von Willebrand Factor A1 Domain Resolves Leukocyte Recruitment and Vascular Leakage during Inflammation\u2014Brief Report","volume":"37","author":"Adam","year":"2017","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1111\/j.1538-7836.2012.04822.x","article-title":"ADAMTS13 reduces VWF-mediated acute inflammation following focal cerebral ischemia in mice: Role of ADAMTS13 and VWF in inflammatory brain injury","volume":"10","author":"Khan","year":"2012","journal-title":"J. Thromb. Haemost."},{"key":"ref_32","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_33","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1056\/NEJMoa022831","article-title":"Acquired von Willebrand Syndrome in Aortic Stenosis","volume":"349","author":"Vincentelli","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"236","DOI":"10.3324\/haematol.10457","article-title":"The relationship between ABO groups and subgroups, factor VIII and von Willebrand factor","volume":"92","author":"Sousa","year":"2007","journal-title":"Haematologica"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1046\/j.1468-0734.2001.00048.x","article-title":"von Willebrand Factor and von Willebrand disease","volume":"5","author":"Budde","year":"2001","journal-title":"Rev. Clin. Exp. Hematol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1477-9560-5-14","article-title":"Relationship between ABO blood group and von Willebrand factor levels: From biology to clinical implications","volume":"5","author":"Franchini","year":"2007","journal-title":"Thromb. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1182\/blood.V69.6.1691.1691","article-title":"The effect of ABO blood group on the diagnosis of von Willebrand disease","volume":"69","author":"Gill","year":"1987","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"65","DOI":"10.29074\/ascls.30.2.65","article-title":"Laboratory Diagnosis of von Willebrand Disease","volume":"30","author":"Smith","year":"2017","journal-title":"Clin. Lab. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"215","DOI":"10.5482\/HAMO-13-08-0045","article-title":"Interactions of von Willebrand factor and ADAMTS13 in von Willebrand disease and thrombotic thrombocytopenic purpura","volume":"34","author":"Budde","year":"2014","journal-title":"Hamostaseologie"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/ijlh.12345","article-title":"Laboratory diagnosis of von Willebrand disease","volume":"37","author":"Roberts","year":"2015","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1111\/hae.12710","article-title":"The Platelet Function Analyser (PFA)-100 and von Willebrand disease: A story well over 16 years in the making","volume":"21","author":"Favaloro","year":"2015","journal-title":"Haemophilia"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1365-2141.2005.05511.x","article-title":"The role of PFA-100R testing in the investigation and management of haemostatic defects in children and adults","volume":"130","author":"Harrison","year":"2005","journal-title":"Br. J. Haematol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1080\/09537104.2017.1306042","article-title":"Flow chamber and microfluidic approaches for measuring thrombus formation in genetic bleeding disorders","volume":"28","author":"Schoeman","year":"2017","journal-title":"Platelets"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1111\/j.1538-7836.2008.02917.x","article-title":"Acquired von Willebrand syndrome: Is it an extremely rare disorder or do we see only the tip of the iceberg?","volume":"6","author":"Federici","year":"2008","journal-title":"J. Thromb. Haemost."},{"key":"ref_45","unstructured":"Rizzo, C., and Rizzo, S. (2012). Thrombotic thrombocytopenic purpura: A review of the literature in the light of our experience with plasma exchange. Blood Transfus."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1055\/s-0034-1376883","article-title":"Inherited and Acquired Thrombotic Thrombocytopenic Purpura (TTP) in Adults","volume":"40","year":"2014","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1056\/NEJMoa1806311","article-title":"Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura","volume":"380","author":"Scully","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1056\/NEJM195807242590416","article-title":"Gastrointestinal Bleeding in Aortic Stenosis","volume":"259","author":"Heyde","year":"1958","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/0140-6736(92)92434-H","article-title":"Aortic stenosis and bleeding gastrointestinal angiodysplasia: Is acquired von Willebrand\u2019s disease the link?","volume":"340","author":"Warkentin","year":"1992","journal-title":"Lancet"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1056\/NEJM200209123471122","article-title":"Gastrointestinal Angiodysplasia and Aortic Stenosis","volume":"347","author":"Warkentin","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1177\/1076029616660759","article-title":"Severe Aortic Valve Stenosis: Sustained Cure of Acquired von Willebrand Syndrome after Surgical Valve Replacement","volume":"23","author":"Frank","year":"2017","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1160\/TH09-06-0391","article-title":"Loss of high-molecular-weight von Willebrand factor multimers mainly affects platelet aggregation in patients with aortic stenosis","volume":"103","author":"Panzer","year":"2010","journal-title":"Thromb. Haemost."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/joic.12478","article-title":"Von Willebrand factor revisited","volume":"31","author":"Yasar","year":"2018","journal-title":"J. Interven. Cardiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1056\/NEJMoa1505643","article-title":"Von Willebrand Factor Multimers during Transcatheter Aortic-Valve Replacement","volume":"375","author":"Rauch","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1093\/bja\/aeq413","article-title":"Acquired type 2A von Willebrand syndrome caused by aortic valve disease corrects during valve surgery","volume":"106","author":"Solomon","year":"2011","journal-title":"Br. J. Anaesth."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1111\/jth.12734","article-title":"Shear stress-associated acquired von Willebrand syndrome in patients with mitral regurgitation","volume":"12","author":"Blackshear","year":"2014","journal-title":"J. Thromb. Haemost."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1182\/blood.V106.11.1790.1790","article-title":"Severe Aortic and Mitral Valve Regurgitation Are Associated with von Willebrand Factor Defect","volume":"106","author":"Susen","year":"2005","journal-title":"Blood"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"219","DOI":"10.4065\/mcp.2010.0309","article-title":"Hypertrophic Obstructive Cardiomyopathy, Bleeding History, and Acquired von Willebrand Syndrome: Response to Septal Myectomy","volume":"86","author":"Blackshear","year":"2011","journal-title":"Mayo Clin. Proc."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1161\/CIRCULATIONAHA.108.786681","article-title":"Functional Impairment of von Willebrand Factor in Hypertrophic Cardiomyopathy: Relation to Rest and Exercise Obstruction","volume":"118","author":"Susen","year":"2008","journal-title":"Circulation"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3133","DOI":"10.1182\/blood-2015-10-636480","article-title":"Acquired von Willebrand syndrome associated with left ventricular assist device","volume":"127","author":"Nascimbene","year":"2016","journal-title":"Blood"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1161\/01.ATV.10.3.449","article-title":"von Willebrand factor and occlusive arterial thrombosis. A study in normal and von Willebrand\u2019s disease pigs with diet-induced hypercholesterolemia and atherosclerosis","volume":"10","author":"Nichols","year":"1990","journal-title":"Arteriosclerosis"},{"key":"ref_62","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_63","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1111\/jth.13142","article-title":"Does deficiency of von Willebrand factor protect against cardiovascular disease? Analysis of a national discharge register","volume":"13","author":"Seaman","year":"2015","journal-title":"J. Thromb. Haemost."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.3892\/mmr.2012.1037","article-title":"Correlation of von Willebrand factor gene polymorphism and coronary heart disease","volume":"6","author":"Xu","year":"2012","journal-title":"Mol. Med. Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1056\/NEJM199503093321003","article-title":"Hemostatic Factors and the Risk of Myocardial Infarction or Sudden Death in Patients with Angina Pectoris","volume":"332","author":"Thompson","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Willeit, P., Thompson, A., Aspelund, T., Rumley, A., Eiriksdottir, G., Lowe, G., Gudnason, V., and Di Angelantonio, E. (2013). Hemostatic Factors and Risk of Coronary Heart Disease in General Populations: New Prospective Study and Updated Meta-Analyses. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055175"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1093\/eurheartj\/ehi104","article-title":"Predictors of the rise in vWF after ST elevation myocardial infarction: Implications for treatment strategies and clinical outcome","volume":"26","author":"Ray","year":"2005","journal-title":"Eur. Heart J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1136\/hrt.66.5.351","article-title":"von Willebrand factor in plasma: A novel risk factor for recurrent myocardial infarction and death","volume":"66","author":"Jansson","year":"1991","journal-title":"Heart"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1177\/2048872614534388","article-title":"Plasma levels of active von Willebrand factor are increased in patients with first ST-segment elevation myocardial infarction: A multicenter and multiethnic study","volume":"4","author":"Rutten","year":"2015","journal-title":"Eur. Heart J. Acute Cardiovasc. Care"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.1111\/j.1538-7836.2006.02161.x","article-title":"Reduced von Willebrand factor-cleaving protease (ADAMTS13) activity in acute myocardial infarction","volume":"4","author":"Kaikita","year":"2006","journal-title":"J. Thromb. Haemost."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1111\/j.1538-7836.2008.02902.x","article-title":"Evidence that high von Willebrand factor and low ADAMTS-13 levels independently increase the risk of a non-fatal heart attack","volume":"6","author":"Crawley","year":"2008","journal-title":"J. Thromb. Haemost."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1182\/blood-2006-07-038166","article-title":"ADAMTS13 and von Willebrand factor and the risk of myocardial infarction in men","volume":"109","author":"Chion","year":"2007","journal-title":"Blood"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1161\/01.CIR.0000120705.55512.EC","article-title":"Endothelial Cell Markers and the Risk of Coronary Heart Disease: The Prospective Epidemiological Study of Myocardial Infarction (PRIME) Study","volume":"109","author":"Morange","year":"2004","journal-title":"Circulation"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.3892\/etm.2015.2721","article-title":"Plasma von Willebrand factor level is transiently elevated in a rat model of acute myocardial infarction","volume":"10","author":"Li","year":"2015","journal-title":"Exp. Ther. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1053\/euhj.1998.1194","article-title":"Relationship between smoking and cardiovascular risk factors in the development of peripheral arterial disease and coronary artery disease; Edinburgh Artery Study Edinburgh Artery Study","volume":"20","author":"Price","year":"1999","journal-title":"Eur. Heart J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1056\/NEJMoa032804","article-title":"C-Reactive Protein and Other Circulating Markers of Inflammation in the Prediction of Coronary Heart Disease","volume":"350","author":"Danesh","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.amjhyper.2004.09.003","article-title":"High pulse pressure and nondipping circadian blood pressure in patients with coronary artery disease: Relationship to thrombogenesis and endothelial damage\/dysfunction","volume":"18","author":"Lee","year":"2005","journal-title":"Am. J. Hypertens."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1016\/S0002-9149(97)00749-2","article-title":"Relation of Endothelium, Thrombogenesis, and Hemorheology in Systemic Hypertension to Ethnicity and Left Ventricular Hypertrophy","volume":"80","author":"Lip","year":"1997","journal-title":"Am. J. Cardiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.1161\/01.ATV.19.12.3071","article-title":"von Willebrand Factor, C-Reactive Protein, and 5-Year Mortality in Diabetic and Nondiabetic Subjects: The Hoorn Study","volume":"19","author":"Jager","year":"1999","journal-title":"Arter. Thromb. Vasc. Biol"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/0140-6736(92)91401-S","article-title":"Urinary albumin excretion, cardiovascular disease, and endothelial dysfunction in non-insulin-dependent diabetes mellitus","volume":"340","author":"Stehouwer","year":"1992","journal-title":"Lancet"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12959-017-0151-3","article-title":"vWF\/ADAMTS13 is associated with on-aspirin residual platelet reactivity and clinical outcome in patients with stable coronary artery disease","volume":"15","author":"Warlo","year":"2017","journal-title":"Thromb. J."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1093\/rheumatology\/34.9.814","article-title":"Altered levels of soluble adhesion molecules in rheumatoid arthritis, vasculitis and systemic sclerosis","volume":"34","author":"Blann","year":"1995","journal-title":"Rheumatology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e000162","DOI":"10.1136\/lupus-2016-000162","article-title":"Increased von Willebrand factor levels in patients with systemic lupus erythematosus reflect inflammation rather than increased propensity for platelet activation","volume":"3","author":"Nossent","year":"2016","journal-title":"Lupus Sci. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1046\/j.1523-1755.2000.00988.x","article-title":"Association between high von Willebrand factor levels and the Thr789Ala vWF gene polymorphism but not with nephropathy in type I diabetes","volume":"57","author":"Lacquemant","year":"2000","journal-title":"Kidney Int."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1161\/01.ATV.0000051384.43104.FC","article-title":"Endothelial Dysfunction: A Marker of Atherosclerotic Risk","volume":"23","author":"Bonetti","year":"2003","journal-title":"ATVB"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1177\/000331970405500210","article-title":"Prospective Evaluation of von Willebrand Factor Release after Multiple and Single Stenting","volume":"55","author":"Heper","year":"2004","journal-title":"Angiology"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1097\/00019501-200512000-00009","article-title":"Time course of release of inflammatory markers after coronary stenting: Comparison between bare metal stent and sirolimus-eluting stent","volume":"16","author":"Kefer","year":"2005","journal-title":"Coron. Artery Dis."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/0049-3848(89)90317-4","article-title":"von Willebrand factor is an acute phase reactant in man","volume":"53","author":"Pottinger","year":"1989","journal-title":"Thromb. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1111\/j.1538-7836.2005.01122.x","article-title":"Platelets adhered to endothelial cell-bound ultra-large von Willebrand factor strings support leukocyte tethering and rolling under high shear stress","volume":"3","author":"Bernardo","year":"2005","journal-title":"J. Thromb. Haemost."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1172\/JCI9516","article-title":"Vasopressin-induced von Willebrand factor secretion from endothelial cells involves V2 receptors and cAMP","volume":"106","author":"Kaufmann","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"ehz747.0326","DOI":"10.1093\/eurheartj\/ehz747.0326","article-title":"P721Shear stress induced unfolding of von willebrand factor may be involved in the premature development of myocardial infarction","volume":"40","author":"Melnikov","year":"2019","journal-title":"Eur. Heart J."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1172\/JCI115198","article-title":"Heparin inhibition of von Willebrand factor-dependent platelet function in vitro and in vivo","volume":"87","author":"Sobel","year":"1991","journal-title":"J. Clin. Investig."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1161\/01.CIR.98.4.294","article-title":"Early Increase of von Willebrand Factor Predicts Adverse Outcome in Unstable Coronary Artery Disease: Beneficial Effects of Enoxaparin","volume":"98","author":"Montalescot","year":"1998","journal-title":"Circulation"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0014-2999(02)01590-X","article-title":"Effect of a humanized monoclonal antibody to von Willebrand factor in a canine model of coronary arterial thrombosis","volume":"443","author":"Kageyama","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2678","DOI":"10.1161\/CIRCULATIONAHA.107.724864","article-title":"First-in-Human Evaluation of Anti\u2013von Willebrand Factor Therapeutic Aptamer ARC1779 in Healthy Volunteers","volume":"116","author":"Gilbert","year":"2007","journal-title":"Circulation"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1161\/STROKEAHA.111.616649","article-title":"The von Willebrand Inhibitor ARC1779 Reduces Cerebral Embolization after Carotid Endarterectomy: A Randomized Trial","volume":"42","author":"Markus","year":"2011","journal-title":"Stroke"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"11180","DOI":"10.1038\/s41598-020-68125-9","article-title":"The aptamer BT200 effectively inhibits von Willebrand factor (VWF) dependent platelet function after stimulated VWF release by desmopressin or endotoxin","volume":"10","author":"Kovacevic","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_98","unstructured":"Sakai, K., Someya, T., Harada, K., Yagi, H., Matsui, T., and Matsumoto, M. (2019). Novel aptamer to von Willebrand factor A1 domain (TAGX-0004) shows total inhibition of thrombus formation superior to ARC1779 and comparable to caplacizumab. Haematologica."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1160\/TH10-12-0804","article-title":"The in vitro effect of the new antithrombotic drug candidate ALX-0081 on blood samples of patients undergoing percutaneous coronary intervention","volume":"106","author":"Simoons","year":"2011","journal-title":"Thromb. Haemost"},{"key":"ref_100","first-page":"A15084","article-title":"Abstract 15084: Safety and Efficacy of Anti-von Willebrand Factor Nanobody\u00ae ALX-0081 in Stable Angina Patients Undergoing Percutaneous Coronary Intervention","volume":"122","author":"Bartunek","year":"2010","journal-title":"Circulation"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s12265-012-9435-y","article-title":"Novel Antiplatelet Agents: ALX-0081, a Nanobody Directed towards von Willebrand Factor","volume":"6","author":"Bartunek","year":"2013","journal-title":"J. Cardiovasc. Trans. Res."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Witsch, T., Martinod, K., Sorvillo, N., Portier, I., De Meyer, S.F., and Wagner, D.D. (2018). Recombinant Human ADAMTS13 Treatment Improves Myocardial Remodeling and Functionality after Pressure Overload Injury in Mice. JAHA, 7.","DOI":"10.1161\/JAHA.117.007004"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/20\/7804\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:25:38Z","timestamp":1760178338000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/20\/7804"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,21]]},"references-count":102,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["ijms21207804"],"URL":"https:\/\/doi.org\/10.3390\/ijms21207804","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,21]]}}}