{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T15:02:55Z","timestamp":1785250975345,"version":"3.55.0"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Cardiac fibrosis is a hallmark of heart failure and can be quantified by the extracellular volume fraction (ECV) derived from diagnostic imaging. However, noninvasive assessment is limited by the lack of specific circulating biomarkers. Recent large plasma proteome analyses have identified SVEP1 (Sushi, von Willebrand factor type A, EGF, and pentraxin domain containing 1) as candidate molecules reflecting cardiac fibrosis. This study aimed to evaluate SVEP1 as a biomarker for cardiac fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      In 72 patients with heart failure due to aortic stenosis, computed tomography\u2010based ECV, serum SVEP1, and BNP (brain natriuretic peptide) levels were assessed. Multivariable regression was used to determine independent predictors of ECV. Publicly available single\u2010nucleus RNA sequencing of human hearts revealed the cellular origin of\n                      <jats:italic toggle=\"no\">SVEP1<\/jats:italic>\n                      . SVEP1 secretion was assessed in human cardiac fibroblasts after TGF\u2010\u03b2 (transforming growth factor\u2010\u03b2) stimulation or small interfering RNA knockdown. Plasma Svep1 and cardiac hydroxyproline levels were measured in mice with angiotensin II\u2010 and phenylephrine\u2010induced cardiac fibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">Serum SVEP1 correlated with ECV and outperformed BNP in detecting fibrosis. Multivariable analysis revealed SVEP1 as an independent predictor of ECV. In addition, snRNA\u2010seq revealed fibroblast\u2010specific expression, expanded in failing hearts consistent with activated fibroblast emergence. Furthermore, TGF\u2010\u03b2 increased SVEP1 secretion in human cardiac fibroblasts, whereas its knockdown reduced SVEP1 secretion. Plasma Svep1 and cardiac hydroxyproline levels were elevated and positively correlated in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Compared with BNP, SVEP1, derived from cardiac fibroblasts, is more strongly associated with ECV\u2010defined fibrosis and may serve as a novel fibrosis\u2010specific circulating biomarker in heart failure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.047119","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T09:16:50Z","timestamp":1777281410000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Sushi, von Willebrand Factor Type A, EGF and Pentraxin Domain\u2010Containing Protein 1: A Novel Fibroblast\u2010Derived Circulating Biomarker Reflecting Cardiac Fibrosis"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8805-8212","authenticated-orcid":false,"given":"Naoya","family":"Kuwahara","sequence":"first","affiliation":[{"name":"Kobe University Graduate School of Medicine","place":["Kobe, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7269-4513","authenticated-orcid":false,"given":"Manabu","family":"Nagao","sequence":"additional","affiliation":[{"name":"Kobe University Graduate School of Medicine","place":["Kobe, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2688-3468","authenticated-orcid":false,"given":"Yu","family":"Izawa","sequence":"additional","affiliation":[{"name":"Kobe University Graduate School of Medicine","place":["Kobe, 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