{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:30:53Z","timestamp":1791196253399,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,1,9]],"date-time":"2014-01-09T00:00:00Z","timestamp":1389225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Societ\u00e0 Prodotti Antibiotici"},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009996","name":"Sigma Tau","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009996","id-type":"DOI","asserted-by":"crossref"}]},{"name":"AstraZeneca"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2014,6]]},"abstract":"Abstract<\/jats:title>Objectives<\/jats:title>Experimental studies have shown involvement of W<\/jats:styled-content>nt signalling in heart failure (HF<\/jats:styled-content>). We hypothesized that secreted frizzled\u2010related protein 3 (sFRP<\/jats:styled-content>3), a modulator of W<\/jats:styled-content>nt signalling, is related to the progression of HF<\/jats:styled-content>.<\/jats:p><\/jats:sec>Design<\/jats:title>Circulating sFRP<\/jats:styled-content>3 was measured in 153 HF<\/jats:styled-content> patients and compared with 25 healthy controls. The association of sFRP<\/jats:styled-content>3 with mortality was evaluated in 1202 patients (GISSI<\/jats:styled-content>\u2010HF<\/jats:styled-content> trial). sFRP<\/jats:styled-content>3 mRNA<\/jats:styled-content> expression was assessed in failing human and murine left ventricles (LV<\/jats:styled-content>), and cellular localization was determined after fractioning of myocardial tissue. In vitro<\/jats:italic> studies were carried out in cardiac fibroblasts subjected to cyclic mechanical stretch.<\/jats:p><\/jats:sec>Results<\/jats:title>(i) Heart failure patients had significantly raised serum sFRP<\/jats:styled-content>3 levels compared with controls, (ii) during a median follow\u2010up of 47\u00a0months, 315 patients died in the GISSI<\/jats:styled-content>\u2010HF<\/jats:styled-content> substudy. In univariable C<\/jats:styled-content>ox regression, tertiles of baseline sFRP<\/jats:styled-content>3 concentration were significantly associated with all\u2010cause and cardiovascular mortality. After adjustment for demographic and clinical variables, but not for CRP<\/jats:styled-content> and NT<\/jats:styled-content>\u2010proBNP<\/jats:styled-content>, the associations with mortality remained significant for the third tertile (all\u2010cause, HR<\/jats:styled-content> 1.45, P\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.011; cardiovascular, HR<\/jats:styled-content> 1.66, P\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.003), (iii) sFRP<\/jats:styled-content>3 mRNA<\/jats:styled-content> expression was increased in failing human LV<\/jats:styled-content>, with a decline following LV<\/jats:styled-content> assist device therapy. LV<\/jats:styled-content> from post\u2010MI<\/jats:styled-content> mice showed an increased sFRP<\/jats:styled-content>3 mRNA<\/jats:styled-content> level, particularly in cardiac fibroblasts, and (iv) mechanical stretch enhanced sFRP<\/jats:styled-content>3 expression and release in myocardial fibroblasts.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>There is an association between increased sFRP<\/jats:styled-content>3 expression and adverse outcome in HF<\/jats:styled-content>, suggesting that the failing myocardium itself contributes to an increase in circulating sFRP<\/jats:styled-content>3.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.12175","type":"journal-article","created":{"date-parts":[[2013,12,10]],"date-time":"2013-12-10T18:34:47Z","timestamp":1386700487000},"page":"621-630","source":"Crossref","is-referenced-by-count":45,"title":["The cardiokine secreted F<\/scp>rizzled\u2010related protein 3, a modulator of W<\/scp>nt signalling, in clinical and experimental heart failure"],"prefix":"10.1111","volume":"275","author":[{"given":"E. T.","family":"Askevold","sequence":"first","affiliation":[{"name":"Research Institute of Internal Medicine Oslo University Hospital Rikshospitalet Oslo Norway"},{"name":"Department of Cardiology Oslo University Hospital Rikshospitalet Oslo Norway"},{"name":"Center for Heart Failure Research University of Oslo Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Aukrust","sequence":"additional","affiliation":[{"name":"Research Institute of Internal Medicine Oslo University Hospital Rikshospitalet Oslo Norway"},{"name":"Section of Clinical Immunology and Infectious Diseases Oslo University Hospital Rikshospitalet Oslo Norway"},{"name":"Faculty of Medicine University of Oslo Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. H.","family":"Nymo","sequence":"additional","affiliation":[{"name":"Research Institute of Internal Medicine Oslo University Hospital Rikshospitalet Oslo Norway"},{"name":"Center for Heart Failure Research University of Oslo Oslo Norway"},{"name":"Faculty of Medicine University of Oslo Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. G.","family":"Lunde","sequence":"additional","affiliation":[{"name":"Center for Heart Failure Research University of Oslo Oslo Norway"},{"name":"Institute for Experimental Medical Research Oslo University Hospital Ullev\u00e5l University of Oslo Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O. J.","family":"Kaasb\u00f8ll","sequence":"additional","affiliation":[{"name":"Center for Heart Failure Research University of Oslo Oslo Norway"},{"name":"Institute for Surgical Research Oslo University Hospital Rikshospitalet Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Aakhus","sequence":"additional","affiliation":[{"name":"Department of Cardiology Oslo University Hospital Rikshospitalet Oslo Norway"},{"name":"Center for Heart Failure Research University of Oslo Oslo Norway"},{"name":"Faculty of Medicine University of Oslo Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Florholmen","sequence":"additional","affiliation":[{"name":"Center for Heart Failure Research University of Oslo Oslo Norway"},{"name":"Institute for Surgical Research Oslo University Hospital Rikshospitalet Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. 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E.","family":"Strand","sequence":"additional","affiliation":[{"name":"Center for Heart Failure Research University of Oslo Oslo Norway"},{"name":"Institute for Experimental Medical Research Oslo University Hospital Ullev\u00e5l University of Oslo Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Attramadal","sequence":"additional","affiliation":[{"name":"Center for Heart Failure Research University of Oslo Oslo Norway"},{"name":"Institute for Surgical Research Oslo University Hospital Rikshospitalet Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Fiane","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Oslo Oslo Norway"},{"name":"Department of Cardiothoracic Surgery Oslo University Hospital Rikshospitalet Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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