{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T08:06:45Z","timestamp":1791446805665,"version":"4.3.3"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T00:00:00Z","timestamp":1585872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","award":["2017_A32"],"award-info":[{"award-number":["2017_A32"]}],"id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","award":["Berlin Institute of Health"],"award-info":[{"award-number":["Berlin Institute of Health"]}],"id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","award":["Sonnenfeld-foundation"],"award-info":[{"award-number":["Sonnenfeld-foundation"]}],"id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["AL2054\/1-1"],"award-info":[{"award-number":["AL2054\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["VO2259\/2-1"],"award-info":[{"award-number":["VO2259\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010447","name":"DZHK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010447","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011102","name":"European Union Seventh Framework Programme","doi-asserted-by":"publisher","award":["FP7\/2007-2013\u2013603288-SysVasc"],"award-info":[{"award-number":["FP7\/2007-2013\u2013603288-SysVasc"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015699","name":"Fresenius Medical Care","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015699","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bundesministerium f\u00fcr Bildung"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Uromodulin is produced exclusively in the kidney and secreted into both urine and blood. Serum levels of uromodulin are correlated with kidney function and reduced in chronic kidney disease (CKD) patients, but physiological functions of serum uromodulin are still elusive. This study investigated the role of uromodulin in medial vascular calcification, a key factor associated with cardiovascular events and mortality in CKD patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results\u2003<\/jats:title>\n                  <jats:p>Experiments were performed in primary human (HAoSMCs) and mouse (MOVAS) aortic smooth muscle cells, cholecalciferol overload and subtotal nephrectomy mouse models and serum from CKD patients. In three independent cohorts of CKD patients, serum uromodulin concentrations were inversely correlated with serum calcification propensity. Uromodulin supplementation reduced phosphate-induced osteo-\/chondrogenic transdifferentiation and calcification of HAoSMCs. In human serum, pro-inflammatory cytokines tumour necrosis factor \u03b1 (TNF\u03b1) and interleukin-1\u03b2 (IL-1\u03b2) co-immunoprecipitated with uromodulin. Uromodulin inhibited TNF\u03b1 and IL-1\u03b2-induced osteo-\/chondrogenic signalling and activation of the transcription factor nuclear factor kappa-light-chain-enhancer of activated \u03b2 cells (NF-kB) as well as phosphate-induced NF-kB-dependent transcriptional activity in HAoSMCs. In vivo, adeno-associated virus (AAV)-mediated overexpression of uromodulin ameliorated vascular calcification in mice with cholecalciferol overload. Conversely, cholecalciferol overload-induced vascular calcification was aggravated in uromodulin-deficient mice. In contrast, uromodulin overexpression failed to reduce vascular calcification during renal failure in mice. Carbamylated uromodulin was detected in serum of CKD patients and uromodulin carbamylation inhibited its anti-calcific properties in vitro.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions\u2003<\/jats:title>\n                  <jats:p>Uromodulin counteracts vascular osteo-\/chondrogenic transdifferentiation and calcification, at least in part, through interference with cytokine-dependent pro-calcific signalling. In CKD, reduction and carbamylation of uromodulin may contribute to vascular pathology.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvaa081","type":"journal-article","created":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T11:07:09Z","timestamp":1585566429000},"page":"930-941","source":"Crossref","is-referenced-by-count":73,"title":["Circulating uromodulin inhibits vascular calcification by interfering with pro-inflammatory cytokine signalling"],"prefix":"10.1093","volume":"117","author":[{"given":"Ioana","family":"Alesutan","sequence":"first","affiliation":[{"name":"Institute for Physiology and Pathophysiology, Johannes Kepler University Linz, Altenberger Strasse 69, 4040 Linz, Austria"},{"name":"Department of Internal Medicine and Cardiology, Campus Virchow-Klinikum, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health (BIH), Anna-Louisa-Karsch 2, 10178 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Berlin, Hessische Strasse 3-4, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trang T D","family":"Luong","sequence":"additional","affiliation":[{"name":"Institute for Physiology and Pathophysiology, Johannes Kepler University Linz, Altenberger Strasse 69, 4040 Linz, Austria"},{"name":"Department of Internal Medicine and Cardiology, Campus Virchow-Klinikum, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadeshda","family":"Schelski","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Campus Virchow-Klinikum, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaber","family":"Masyout","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Campus Virchow-Klinikum, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Hille","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University of Kiel, Arnold-Heller-Str. 3, 24105 Kiel, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Hamburg\/Kiel\/L\u00fcbeck, Martinistr. 52, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5265-8088","authenticated-orcid":false,"given":"Markus P","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), Ulmenweg 18, 91054 Erlangen, Germany"},{"name":"German Chronic Kidney Disease (GCKD) Study"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7328-4708","authenticated-orcid":false,"given":"Delyth","family":"Graham","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Zickler","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Medical Intensive Care, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Verheyen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misael","family":"Estepa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Campus Virchow-Klinikum, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Pasch","sequence":"additional","affiliation":[{"name":"Institute for Physiology and Pathophysiology, Johannes Kepler University Linz, Altenberger Strasse 69, 4040 Linz, Austria"},{"name":"Calciscon AG, Aarbergstrasse 5, 2560 Nidau-Biel, Switzerland"},{"name":"Nierenpraxis Bern, Bubenbergplatz 5, 3011 Bern, Switzerland"},{"name":"Department of Nephrology, Lindenhofspital, Bremgartenstrasse 117, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winfried","family":"Maerz","sequence":"additional","affiliation":[{"name":"Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria"},{"name":"Medical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Ludolf Krehl Street 7-11, 68167 Mannheim, Germany"},{"name":"Synlab Academy, SYNLAB Holding Deutschland GmbH, P5,7, 68161 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Tomaschitz","sequence":"additional","affiliation":[{"name":"Health Center Trofaiach, G\u00f6ssgrabenstrasse 2a, 8739 Trofaiach, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Pilz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Frey","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University of Kiel, Arnold-Heller-Str. 3, 24105 Kiel, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Hamburg\/Kiel\/L\u00fcbeck, Martinistr. 52, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Eberhard-Karls University, Wilhelmstr. 56, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2238-2612","authenticated-orcid":false,"given":"Christian","family":"Delles","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Voelkl","sequence":"additional","affiliation":[{"name":"Institute for Physiology and Pathophysiology, Johannes Kepler University Linz, Altenberger Strasse 69, 4040 Linz, Austria"},{"name":"Department of Internal Medicine and Cardiology, Campus Virchow-Klinikum, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Berlin, Hessische Strasse 3-4, 10115 Berlin, Germany"},{"name":"Department of Nephrology and Medical Intensive Care, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,4,3]]},"reference":[{"key":"2021022213490499500_cvaa081-B1","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3181\/00379727-74-17825","article-title":"Characterization and separation of an inhibitor of viral hemagglutination present in urine","volume":"74","author":"Tamm","year":"1950","journal-title":"Proc Soc Exp Biol Med"},{"key":"2021022213490499500_cvaa081-B2","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1042\/bj1810525","article-title":"Localization by immunofluorescence and by light- and electron-microscopic immunoperoxidase techniques of Tamm-Horsfall glycoprotein in adult hamster kidney","volume":"181","author":"Sikri","year":"1979","journal-title":"Biochem J"},{"key":"2021022213490499500_cvaa081-B3","doi-asserted-by":"crossref","first-page":"2998","DOI":"10.1093\/hmg\/ddq205","article-title":"A transgenic mouse model for 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