{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T20:12:20Z","timestamp":1767211940942},"reference-count":52,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,3,1]]},"abstract":"<jats:p>CKD (chronic kidney disease) is a life-threatening pathology, often requiring HD (haemodialysis) and characterized by high OS (oxidative stress), inflammation and perturbation of vascular endothelium. HD patients have increased levels of vWF (von Willebrand factor), a large protein (~240\u00a0kDa) released as UL-vWF (ultra large-vWF polymers, molecular mass ~20000\u201350000\u00a0kDa) from vascular endothelial cells and megakaryocytes, and responsible for the initiation of primary haemostasis. The pro-haemostatic potential of vWF increases with its length, which is proteolytically regulated by ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin motifs 13), a zinc-protease cleaving vWF at the single Tyr1605\u2013Met1606 bond, and by LSPs (leucocyte serine proteases), released by activated PMNs (polymorphonuclear cells) during bacterial infections. Previous studies have shown that in vitro oxidation of Met1606 hinders vWF cleavage by ADAMTS-13, resulting in the accumulation of UL-vWF that are not only more pro-thrombotic than shorter vWF oligomers, but also more efficient in binding to bacterial adhesins during sepsis. Notably, HD patients have increased risk of developing dramatic cardiovascular and septic complications, whose underlying mechanisms are largely unknown. In the present study, we first purified vWF from HD patients and then chemically characterized its oxidative state. Interestingly, HD-vWF contains high carbonyl levels and increased proportion of UL-vWF polymers that are also more resistant to ADAMTS-13. Using TMS (targeted MS) techniques, we estimated that HD-vWF contains &amp;gt;10% of Met1606 in the sulfoxide form. We conclude that oxidation of Met1606, impairing ADAMTS-13 cleavage, results in the accumulation of UL-vWF polymers, which recruit and activate platelets more efficiently and bind more tightly to bacterial adhesins, thus contributing to the development of thrombotic and septic complications in CKD.<\/jats:p>","DOI":"10.1042\/bj20111798","type":"journal-article","created":{"date-parts":[[2011,11,21]],"date-time":"2011-11-21T09:33:46Z","timestamp":1321868026000},"page":"423-432","update-policy":"http:\/\/dx.doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Oxidation of Met1606 in von Willebrand factor is a risk factor for thrombotic and septic complications in chronic renal failure"],"prefix":"10.1042","volume":"442","author":[{"given":"Vincenzo","family":"De Filippis","sequence":"first","affiliation":[{"name":"Laboratory of Protein Chemistry, Department of Pharmaceutical Sciences, University of Padova, Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Lancellotti","sequence":"additional","affiliation":[{"name":"Haemostasis Research Centre, Institute of Internal Medicine and Geriatrics, Catholic University School of Medicine, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Maset","sequence":"additional","affiliation":[{"name":"Laboratory of Protein Chemistry, Department of Pharmaceutical Sciences, University of Padova, Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Spolaore","sequence":"additional","affiliation":[{"name":"Laboratory of Protein Chemistry, Department of Pharmaceutical Sciences, University of Padova, Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Pozzi","sequence":"additional","affiliation":[{"name":"Laboratory of Protein Chemistry, Department of Pharmaceutical Sciences, University of Padova, Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Gambaro","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Dialysis, Department of Internal Medicine and Medical Specialties, Renal Program, Columbus-Gemelli University Hospital, Catholic University, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Oggianu","sequence":"additional","affiliation":[{"name":"Haemostasis Research Centre, Institute of Internal Medicine and Geriatrics, Catholic University School of Medicine, Rome, Italy"},{"name":"Section of Biology Applied to Human Health, \u2018Roma Tre\u2019 University, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo A.","family":"Cal\u00f2","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine and Postgraduate School of Nephrology, University of Padova, Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raimondo","family":"De Cristofaro","sequence":"additional","affiliation":[{"name":"Haemostasis Research Centre, Institute of Internal Medicine and Geriatrics, Catholic University School of Medicine, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2012,2,13]]},"reference":[{"key":"2021112215320129800_B1","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1056\/NEJMoa041031","article-title":"Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization","volume":"351","author":"Go","year":"2004","journal-title":"N. 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