{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T12:03:53Z","timestamp":1770897833581,"version":"3.50.1"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"vor","delay-in-days":2116,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T00:00:00Z","timestamp":1585872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Heart failure (HF) is frequently caused by an ischaemic event (e.g. myocardial infarction) but might also be caused by a primary disease of the myocardium (cardiomyopathy). In order to identify targeted therapies specific for either ischaemic or non-ischaemic HF, it is important to better understand differences in underlying molecular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We performed a biological physical protein\u2013protein interaction network analysis to identify pathophysiological pathways distinguishing ischaemic from non-ischaemic HF. First, differentially expressed plasma protein biomarkers were identified in 1160 patients enrolled in the BIOSTAT-CHF study, 715 of whom had ischaemic HF and 445 had non-ischaemic HF. Second, we constructed an enriched physical protein\u2013protein interaction network, followed by a pathway over-representation analysis. Finally, we identified key network proteins. Data were validated in an independent HF cohort comprised of 765 ischaemic and 100 non-ischaemic HF patients. We found 21\/92 proteins to be up-regulated and 2\/92 down-regulated in ischaemic relative to non-ischaemic HF patients. An enriched network of 18 proteins that were specific for ischaemic heart disease yielded six pathways, which are related to inflammation, endothelial dysfunction superoxide production, coagulation, and atherosclerosis. We identified five key network proteins: acid phosphatase 5, epidermal growth factor receptor, insulin-like growth factor binding protein-1, plasminogen activator urokinase receptor, and secreted phosphoprotein 1. Similar results were observed in the independent validation cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Pathophysiological pathways distinguishing patients with ischaemic HF from those with non-ischaemic HF were related to inflammation, endothelial dysfunction superoxide production, coagulation, and atherosclerosis. The five key pathway proteins identified are potential treatment targets specifically for patients with ischaemic HF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.1811","type":"journal-article","created":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T12:30:45Z","timestamp":1585917045000},"page":"821-833","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["A Network Analysis to Identify Pathophysiological Pathways Distinguishing Ischaemic from Non-Ischaemic Heart Failure"],"prefix":"10.1093","volume":"22","author":[{"given":"Iziah E.","family":"Sama","sequence":"first","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca J.","family":"Woolley","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan F.","family":"Nauta","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon P.R.","family":"Romaine","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, and NIHR Leicester Biomedical Research Centre , Leicester ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasper","family":"Tromp","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]},{"name":"Department of Cardiology, National Heart Centre Singapore \u00a0","place":["Singapore"]},{"name":"Singapore Duke-NUS Graduate Medical School \u00a0","place":["Singapore"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jozine M.","family":"ter Maaten","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics & Clinical Trials Unit, University of Glasgow and Clinical Cardiology, National Heart & Lung Institute, Imperial College London , London ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"van der Meer","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics & Clinical Trials Unit, University of Glasgow and Clinical Cardiology, National Heart & Lung Institute, Imperial College London , London ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolyn S.P.","family":"Lam","sequence":"additional","affiliation":[{"name":"Singapore Duke-NUS Graduate Medical School \u00a0","place":["Singapore"]},{"name":"Robertson Centre for Biostatistics & Clinical Trials Unit, University of Glasgow and Clinical Cardiology, National Heart & Lung Institute, Imperial College London , London ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nilesh J.","family":"Samani","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, and NIHR Leicester Biomedical Research Centre , Leicester ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leong L.","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, and NIHR Leicester Biomedical Research Centre , Leicester ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Metra","sequence":"additional","affiliation":[{"name":"Institute of Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia , Brescia ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth","family":"Dickstein","sequence":"additional","affiliation":[{"name":"University of Bergen , Bergen ,","place":["Norway"]},{"name":"Stavanger University Hospital , Stavanger ,","place":["Norway"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan D.","family":"Anker","sequence":"additional","affiliation":[{"name":"Department of Cardiology (CVK) and Berlin-Brandenburg Center for Regenerative Therapies (BCRT); German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin , Berlin ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"CHU de Nancy, Inserm CIC 1433, Universit\u00e9 de Lorrain, CHRU de Nancy, F-CRIN INI-CRCT , Nancy ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chim C.","family":"Lang","sequence":"additional","affiliation":[{"name":"Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee Ninewells Hospital and Medical School , Dundee ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John G.F.","family":"Cleland","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics & Clinical Trials Unit, University of Glasgow and Clinical Cardiology, National Heart & Lung Institute, Imperial College London , London ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk J.","family":"van Veldhuisen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans L.","family":"Hillege","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriaan A.","family":"Voors","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,4,3]]},"reference":[{"key":"2026011721352698300_ejhf1811-bib-0001","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/ejhf.592","article-title":"2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). 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