{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T13:19:48Z","timestamp":1789046388392,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006636","name":"Forskningsr\u00e5det om H\u00e4lsa, Arbetsliv och V\u00e4lf\u00e4rd","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100006636","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009745","name":"Emil och Wera Cornells Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009745","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008546","name":"Diabetesf\u00f6rbundet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008546","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012774","name":"Innovationsfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013751","name":"Stroke Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013751","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Rupture of atherosclerotic plaques is the major cause of acute cardiovascular events. The biomarker PRO\u2010C6 measuring Endotrophin, a matrikine of collagen type VI, may provide valuable information detecting subjects in need of intensified strategies for secondary prevention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>In this study, we evaluate endotrophin in human atherosclerotic plaques and circulating levels of PRO\u2010C6 in patients with atherosclerosis, to determine the predictive potential of the biomarker.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Sections from the stenotic human carotid plaques were stained with the PRO\u2010C6 antibody. PRO\u2010C6 was measured in serum of patients enrolled in the Carotid Plaque Imagining Project (CPIP) (discovery cohort,\n                      <jats:italic>n\u00a0<\/jats:italic>\n                      =\u00a0577) and the innovative medicines initiative surrogate markers for micro\u2010 and macrovascular hard end\u2010points for innovative diabetes tools (IMI\u2010SUMMIT, validation cohort,\n                      <jats:italic>n\u00a0<\/jats:italic>\n                      =\u00a01,378). Median follow\u2010up was 43\u00a0months. Kaplan\u2013Meier curves and log\u2010rank tests were performed in the discovery cohort. Cox proportional hazard regression analysis (HR with 95% CI) was used in the discovery cohort and binary logistic regression (OR with 95% CI) in the validation cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PRO\u2010C6 was localized in the core and shoulder of the atherosclerotic plaque. In the discovery cohort, PRO\u2010C6 independently predicted future cardiovascular events (HR 1.089 [95% CI 1.019 \u22121.164],\n                      <jats:italic>p\u00a0<\/jats:italic>\n                      =\u00a00.01), cardiovascular death (HR 1.118 [95% CI 1.008 \u22121.241],\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.04) and all\u2010cause death (HR 1.087 [95% CI 1.008 \u22121.172],\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.03). In the validation cohort, PRO\u2010C6 predicted future cardiovascular events (OR 1.063 [95% CI 1.011 \u22121.117],\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.017).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PRO\u2010C6 is present in the atherosclerotic plaque and associated with future cardiovascular events, cardiovascular death and all\u2010cause mortality in two large prospective cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/joim.13253","type":"journal-article","created":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T02:19:28Z","timestamp":1620267568000},"page":"179-189","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["The novel collagen matrikine, endotrophin, is associated with mortality and cardiovascular events in patients with atherosclerosis"],"prefix":"10.1111","volume":"290","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4612-1014","authenticated-orcid":false,"given":"S.","family":"Holm Nielsen","sequence":"first","affiliation":[{"name":"Nordic Bioscience Herlev Denmark"},{"name":"Department of Biomedicine and Biotechnology Technical University of Denmark Lyngby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2691-9192","authenticated-orcid":false,"given":"A.","family":"Edsfeldt","sequence":"additional","affiliation":[{"name":"Department of Cardiology Sk\u00e5ne University Hospital Malm\u00f6 Sweden"},{"name":"Department of Clinical Sciences Lund University Malm\u00f6 Sweden"},{"name":"Wallenberg Center for Molecular Medicine Lund University Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Tengryd","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund University Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Gustafsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund University Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. C.","family":"Shore","sequence":"additional","affiliation":[{"name":"Diabetes and Vascular Medicine University of Exeter, Medical School National Institute for Health Research Exeter Clinical Research Facility Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Natali","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Pisa Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Khan","sequence":"additional","affiliation":[{"name":"Division of Molecular and Clinical medicine University of Dundee Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Genovese","sequence":"additional","affiliation":[{"name":"Nordic Bioscience Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7075-1772","authenticated-orcid":false,"given":"E.","family":"Bengtsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund University Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Karsdal","sequence":"additional","affiliation":[{"name":"Nordic Bioscience Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. J.","family":"Leeming","sequence":"additional","affiliation":[{"name":"Nordic Bioscience Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9752-7479","authenticated-orcid":false,"given":"J.","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund University Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Goncalves","sequence":"additional","affiliation":[{"name":"Department of Cardiology Sk\u00e5ne University Hospital Malm\u00f6 Sweden"},{"name":"Department of Clinical Sciences Lund University Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.04.052"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx143"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.303414"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)01767-9"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.12.4.494"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.169748"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M510192200"},{"issue":"3485","key":"e_1_2_10_9_1","first-page":"1","article-title":"Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction","volume":"5","author":"Sun K","year":"2014","journal-title":"Nat Commun"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.218"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.6227"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0144525"},{"issue":"1","key":"e_1_2_10_13_1","first-page":"1","article-title":"Urinary endotrophin predicts disease progression in patients with chronic kidney disease","volume":"7","author":"Guldager D","year":"2017","journal-title":"Sci Rep"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0175200"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0000000000000112"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12819"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-23458-4"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc17-2392"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2017.07.014"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.13034"},{"key":"e_1_2_10_21_1","doi-asserted-by":"crossref","first-page":"3061","DOI":"10.1093\/eurheartj\/ehz746.0179","article-title":"Acute cardiac fibrogenic response triggered by endotrophin, a type VI collagen signalling molecule","volume":"40","author":"Reese\u2010Petersen A","year":"2019","journal-title":"Eur Heart J"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-016-4094-1"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/2048872612441582"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2018.02.005"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01300-08"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0175898"},{"issue":"9","key":"e_1_2_10_27_1","first-page":"1","article-title":"Human endotrophin as a driver of malignant tumor growth","volume":"5","author":"Bu D","year":"2019","journal-title":"JCI insight"}],"container-title":["Journal of Internal Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/joim.13253","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/joim.13253","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/joim.13253","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T05:03:25Z","timestamp":1693371805000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/joim.13253"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,5]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1111\/joim.13253"],"URL":"https:\/\/doi.org\/10.1111\/joim.13253","archive":["Portico"],"relation":{},"ISSN":["0954-6820","1365-2796"],"issn-type":[{"value":"0954-6820","type":"print"},{"value":"1365-2796","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,5]]},"assertion":[{"value":"2020-10-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}