{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T08:37:55Z","timestamp":1782549475812,"version":"3.54.5"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":1988,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,7,10]],"date-time":"2020-07-10T00:00:00Z","timestamp":1594339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001722","name":"KNAW","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001722","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Queen of Hearts"},{"name":"National Medical Research Council CS-IRG"},{"name":"ATTRaCT SPF"},{"name":"National Medical Research Council Center Grant"},{"DOI":"10.13039\/501100001352","name":"National University of Singapore","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001352","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001722","name":"Koninklijke Nederlandse Akademie van Wetenschappen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001722","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001352","name":"National University of Singapore","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001352","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Extracellular vesicles (EVs) are small double-membrane plasma vesicles that play key roles in cellular crosstalk and mechanisms such as inflammation. The role of EVs in combined organ failure such as cardiorenal syndrome has not been investigated. The aim of this study is to identify EV proteins that are associated with renal dysfunction, heart failure, and their combination in dyspnoeic patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Blood samples were prospectively collected in 404 patients presenting with breathlessness at the emergency department at National University Hospital, Singapore. Renal dysfunction was defined as estimated glomerular filtration rate &amp;lt; 60 mL\/min\/1.73 m2. The presence of heart failure was independently adjudicated by two clinicians on the basis of the criteria of the European Society of Cardiology guidelines. Protein levels of SerpinG1, SerpinF2, Cystatin C, and CD14 were measured with a quantitative immune assay within three EV sub-fractions and in plasma and were tested for their associations with renal dysfunction, heart failure, and the concurrence of both conditions using multinomial regression analysis, thereby correcting for confounders such as age, gender, ethnicity, and co-morbidities. Renal dysfunction was found in 92 patients (23%), while heart failure was present in 141 (35%). In total, 58 patients (14%) were diagnosed with both renal dysfunction and heart failure. Regression analysis showed that Cystatin C was associated with renal dysfunction, heart failure, and their combination in all three EV sub-fractions and in plasma. CD14 was associated with both renal dysfunction and the combined renal dysfunction and heart failure in all EV sub-fractions, and with presence of heart failure in the high density lipoprotein sub-fraction. SerpinG1 and SerpinF2 were associated with heart failure in, respectively, two and one out of three EV sub-fractions and in plasma, but not with renal dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We provide the first data showing that Cystatin C and CD14 in circulating EVs are associated with both renal dysfunction and heart failure in patients presenting with acute dyspnoea. This suggests that EV proteins may be involved in the combined organ failure of the cardiorenal syndrome and may represent possible targets for prevention or treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.12699","type":"journal-article","created":{"date-parts":[[2020,7,10]],"date-time":"2020-07-10T06:45:01Z","timestamp":1594363501000},"page":"2240-2249","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Extracellular Vesicle Cystatin C and CD14 are Associated with Both Renal Dysfunction and Heart Failure"],"prefix":"10.1093","volume":"7","author":[{"given":"Laura","family":"Verbree-Willemsen","sequence":"first","affiliation":[{"name":"Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University , Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-nan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore \u00a0","place":["Singapore"]},{"name":"Cardiovascular Research Institute, National University Heart Centre Singapore \u00a0","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irwani","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, National University Health System Singapore \u00a0","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirley B.S.","family":"Ooi","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, National University Health System Singapore \u00a0","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiong-Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore \u00a0","place":["Singapore"]},{"name":"Cardiovascular Research Institute, National University Heart Centre Singapore \u00a0","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad I.","family":"Mazlan","sequence":"additional","affiliation":[{"name":"Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore \u00a0","place":["Singapore"]},{"name":"Cardiovascular Research Institute, National University Heart Centre Singapore \u00a0","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Win S.","family":"Kuan","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, National University Health System Singapore \u00a0","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siew-Pang","family":"Chan","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, National University Heart Centre Singapore \u00a0","place":["Singapore"]},{"name":"Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore \u00a0","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda M.","family":"Peelen","sequence":"additional","affiliation":[{"name":"Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University , Utrecht ,","place":["The Netherlands"]},{"name":"Department of Anaesthesiology, University Medical Center Utrecht, Utrecht University , Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diederick E.","family":"Grobbee","sequence":"additional","affiliation":[{"name":"Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University , Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Mark","family":"Richards","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, National University Heart Centre Singapore \u00a0","place":["Singapore"]},{"name":"Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore \u00a0","place":["Singapore"]},{"name":"Christchurch Heart Institute, University of Otago , Christchurch ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn S.P.","family":"Lam","sequence":"additional","affiliation":[{"name":"National Heart Centre Singapore, Duke-NUS Graduate Medical School \u00a0","place":["Singapore"]},{"name":"Department of Cardiology, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique P.V.","family":"de Kleijn*","sequence":"additional","affiliation":[{"name":"Department of Surgery, Yong Loo Lin School of Medicine, National University of 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