{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:05:23Z","timestamp":1790301923004,"version":"4.1.0"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T00:00:00Z","timestamp":1605225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Peptides"],"published-print":{"date-parts":[[2021,2]]},"DOI":"10.1016\/j.peptides.2020.170440","type":"journal-article","created":{"date-parts":[[2020,11,7]],"date-time":"2020-11-07T11:03:23Z","timestamp":1604747003000},"page":"170440","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":14,"special_numbering":"C","title":["Plasma levels of apelin are reduced in patients with liver fibrosis and cirrhosis but are not correlated with circulating levels of bone morphogenetic protein 9 and 10"],"prefix":"10.1016","volume":"136","author":[{"given":"Nicola E.","family":"Owen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duuamene","family":"Nyimanu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhoda E.","family":"Kuc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Upton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas W.","family":"Morrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme J.","family":"Alexander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet J.","family":"Maguire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony P.","family":"Davenport","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.peptides.2020.170440_bib0005","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ab.2013.07.006","article-title":"Pyroglutamyl apelin-13 identified as the major apelin isoform in human plasma","volume":"442","author":"Zhen","year":"2013","journal-title":"Anal. Biochem."},{"issue":"3","key":"10.1016\/j.peptides.2020.170440_bib0010","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1161\/HYPERTENSIONAHA.109.134619","article-title":"[Pyr1]apelin-13 identified as the predominant apelin isoform in the human heart: vasoactive mechanisms and inotropic action in disease","volume":"54","author":"Maguire","year":"2009","journal-title":"Hypertension"},{"issue":"4","key":"10.1016\/j.peptides.2020.170440_bib0015","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1124\/pr.119.017533","article-title":"International Union of Basic and Clinical Pharmacology. CVII. Structure and pharmacology of the apelin receptor with a recommendation that elabela\/toddler is a second endogenous peptide ligand","volume":"71","author":"Read","year":"2019","journal-title":"Pharmacol. Rev."},{"issue":"1","key":"10.1016\/j.peptides.2020.170440_bib0020","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/nyas.14123","article-title":"The apelinergic system: a perspective on challenges and opportunities in cardiovascular and metabolic disorders","volume":"1455","author":"Marsault","year":"2019","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.peptides.2020.170440_bib0025","unstructured":"BLUEPRINT (https:\/\/blueprint.haem.cam.ac.uk\/SingleGene\/)."},{"issue":"5","key":"10.1016\/j.peptides.2020.170440_bib0030","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1111\/j.1872-034X.2011.00945.x","article-title":"Enhanced expressions of apelin on proliferative hepatic arterial capillaries in human cirrhotic liver","volume":"42","author":"Yokomori","year":"2012","journal-title":"Hepatol. Res."},{"issue":"11","key":"10.1016\/j.peptides.2020.170440_bib0035","doi-asserted-by":"crossref","first-page":"5306","DOI":"10.1210\/en.2010-0754","article-title":"Apelin mediates the induction of profibrogenic genes in human hepatic stellate cells","volume":"151","author":"Melgar-Lesmes","year":"2010","journal-title":"Endocrinology"},{"issue":"10","key":"10.1016\/j.peptides.2020.170440_bib0040","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1136\/gut.2010.234690","article-title":"Hypoxia and pro-inflammatory factors upregulate apelin receptor expression in human stellate cells and hepatocytes","volume":"60","author":"Melgar-Lesmes","year":"2011","journal-title":"Gut"},{"issue":"11","key":"10.1016\/j.peptides.2020.170440_bib0045","doi-asserted-by":"crossref","DOI":"10.3390\/cells8111311","article-title":"Roles of the hepatic endocannabinoid and apelin systems in the pathogenesis of liver fibrosis","volume":"8","author":"Melgar-Lesmes","year":"2019","journal-title":"Cells"},{"issue":"1\u20132","key":"10.1016\/j.peptides.2020.170440_bib0050","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s11010-019-03581-0","article-title":"Apelin promotes hepatic fibrosis through ERK signaling in LX-2 cells","volume":"460","author":"Wang","year":"2019","journal-title":"Mol. Cell. Biochem."},{"issue":"4","key":"10.1016\/j.peptides.2020.170440_bib0055","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1002\/hep.22467","article-title":"The hepatic apelin system: a new therapeutic target for liver disease","volume":"48","author":"Principe","year":"2008","journal-title":"Hepatology"},{"issue":"1","key":"10.1016\/j.peptides.2020.170440_bib0060","doi-asserted-by":"crossref","first-page":"109","DOI":"10.5009\/gnl14345","article-title":"Clinical implications of the serum apelin level on portal hypertension and prognosis of liver cirrhosis","volume":"10","author":"Lim","year":"2016","journal-title":"Gut Liver"},{"issue":"10","key":"10.1016\/j.peptides.2020.170440_bib0065","doi-asserted-by":"crossref","first-page":"3020","DOI":"10.3748\/wjg.v21.i10.3020","article-title":"Adipokines levels are associated with the severity of liver disease in patients with alcoholic cirrhosis","volume":"21","author":"Kalafateli","year":"2015","journal-title":"World J. Gastroenterol."},{"issue":"4","key":"10.1016\/j.peptides.2020.170440_bib0070","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.metabol.2010.05.008","article-title":"Serum levels of vaspin, obestatin, and apelin-36 in patients with nonalcoholic fatty liver disease","volume":"60","author":"Aktas","year":"2011","journal-title":"Metabolism"},{"issue":"7","key":"10.1016\/j.peptides.2020.170440_bib0075","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.metabol.2009.10.019","article-title":"Plasma apelin levels in subjects with nonalcoholic fatty liver disease","volume":"59","author":"Ercin","year":"2010","journal-title":"Metabolism"},{"issue":"3","key":"10.1016\/j.peptides.2020.170440_bib0080","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.gendis.2019.07.003","article-title":"The wonders of BMP9: from mesenchymal stem cell differentiation, angiogenesis, neurogenesis, tumorigenesis, and metabolism to regenerative medicine","volume":"6","author":"Mostafa","year":"2019","journal-title":"Genes Dis."},{"issue":"3","key":"10.1016\/j.peptides.2020.170440_bib0085","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1042\/BST20180137","article-title":"Advances in the molecular regulation of endothelial BMP9 signalling complexes and implications for cardiovascular disease","volume":"47","author":"Wood","year":"2019","journal-title":"Biochem. Soc. Trans."},{"key":"10.1016\/j.peptides.2020.170440_bib0090","unstructured":"Human Tissue Atlas (https:\/\/www.proteinatlas.org\/ENSG00000263761-GDF2\/tissue)."},{"issue":"4","key":"10.1016\/j.peptides.2020.170440_bib0095","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1002\/hep.30655","article-title":"Bone morphogenetic protein 9 is a paracrine factor controlling liver sinusoidal endothelial cell fenestration and protecting against hepatic fibrosis","volume":"70","author":"Desroches-Castan","year":"2019","journal-title":"Hepatology"},{"key":"10.1016\/j.peptides.2020.170440_bib0100","unstructured":"Human Tissue Atlas (https:\/\/www.proteinatlas.org\/ENSG00000163217-BMP10\/tissue)."},{"issue":"6","key":"10.1016\/j.peptides.2020.170440_bib0105","doi-asserted-by":"crossref","first-page":"2954","DOI":"10.1074\/jbc.M115.683292","article-title":"The prodomain-bound form of bone morphogenetic protein 10 is biologically active on endothelial cells","volume":"291","author":"Jiang","year":"2016","journal-title":"J. Biol. Chem."},{"issue":"9","key":"10.1016\/j.peptides.2020.170440_bib0110","doi-asserted-by":"crossref","first-page":"3735","DOI":"10.1172\/JCI43382","article-title":"Disruption of PPARgamma\/beta-catenin-mediated regulation of apelin impairs BMP-induced mouse and human pulmonary arterial EC survival","volume":"121","author":"Alastalo","year":"2011","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.peptides.2020.170440_bib0115","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2020.102794","article-title":"Reduced circulating BMP9 and BMP10 and elevated endoglin are associated with disease severity, decompensation and pulmonary vascular syndromes in patients with cirrhosis","volume":"56","author":"Owen","year":"2020","journal-title":"eBiomedicine"},{"issue":"1","key":"10.1016\/j.peptides.2020.170440_bib0120","doi-asserted-by":"crossref","first-page":"19934","DOI":"10.1038\/s41598-019-56157-9","article-title":"Development and validation of an LC-MS\/MS method for detection and quantification of in vivo derived metabolites of [Pyr(1)]apelin-13 in humans","volume":"9","author":"Nyimanu","year":"2019","journal-title":"Sci. Rep."},{"issue":"67","key":"10.1016\/j.peptides.2020.170440_bib0125","doi-asserted-by":"crossref","first-page":"112145","DOI":"10.18632\/oncotarget.22841","article-title":"Apelin\/APJ system: a key therapeutic target for liver disease","volume":"8","author":"Lv","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.peptides.2020.170440_bib0130","doi-asserted-by":"crossref","first-page":"221","DOI":"10.3389\/fphar.2017.00221","article-title":"The role of the apelin\/APJ system in the regulation of liver disease","volume":"8","author":"Lv","year":"2017","journal-title":"Front. Pharmacol."},{"issue":"3","key":"10.1016\/j.peptides.2020.170440_bib0135","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1042\/cs0780261","article-title":"A sensitive radioimmunoassay measuring endothelin-like immunoreactivity in human plasma: comparison of levels in patients with essential hypertension and normotensive control subjects","volume":"78","author":"Davenport","year":"1990","journal-title":"Clin. Sci. (Lond.)"},{"issue":"2","key":"10.1016\/j.peptides.2020.170440_bib0140","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/0196-9781(94)00163-4","article-title":"Neuropeptide FF-like immunoreactivity in human plasma","volume":"16","author":"Sundblom","year":"1995","journal-title":"Peptides"},{"issue":"4","key":"10.1016\/j.peptides.2020.170440_bib0145","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1159\/000337104","article-title":"Apelin, plasmatic osmolality and hypotension in dialysed patients","volume":"33","author":"Cernaro","year":"2012","journal-title":"Blood Purif."},{"key":"10.1016\/j.peptides.2020.170440_bib0150","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.3389\/fneur.2019.01228","article-title":"Diagnostic significance of plasma levels of novel adipokines in patients with symptomatic intra- and extracranial atherosclerotic stenosis","volume":"10","author":"Yu","year":"2019","journal-title":"Front. Neurol."},{"key":"10.1016\/j.peptides.2020.170440_bib0155","doi-asserted-by":"crossref","DOI":"10.1152\/ajpcell.00168.2012","article-title":"Inhibition of apelin expression by BMP signaling in endothelial cells","volume":"303","author":"Poirier","year":"2012","journal-title":"Am. J. Physiol. \u2013 Cell Physiol."},{"key":"10.1016\/j.peptides.2020.170440_bib0160","doi-asserted-by":"crossref","DOI":"10.1152\/ajpcell.00283.2012","article-title":"BMPs go for apelin to regulate angiogenesis. Focus on \u201cInhibition of apelin expression by BMP signaling in endothelial cells\u201d","volume":"303","author":"Ciais","year":"2012","journal-title":"Am. J. Physiol. - Cell Physiol"},{"issue":"2","key":"10.1016\/j.peptides.2020.170440_bib0165","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1007\/s00535-010-0296-3","article-title":"Overexpression of apelin receptor (APJ\/AGTRL1) on hepatic stellate cells and sinusoidal angiogenesis in human cirrhotic liver","volume":"46","author":"Yokomori","year":"2011","journal-title":"J. Gastroenterol."},{"issue":"1","key":"10.1016\/j.peptides.2020.170440_bib0170","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s00383-012-3210-7","article-title":"Apelin is a marker of the progression of liver fibrosis and portal hypertension in patients with biliary atresia","volume":"29","author":"Chen","year":"2013","journal-title":"Pediatr. Surg. Int."},{"issue":"3","key":"10.1016\/j.peptides.2020.170440_bib0175","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1124\/jpet.111.188078","article-title":"Prevention of fibrosis progression in CCl4-treated rats: role of the hepatic endocannabinoid and apelin systems","volume":"340","author":"Reichenbach","year":"2012","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.peptides.2020.170440_bib0180","doi-asserted-by":"crossref","first-page":"92","DOI":"10.3389\/fnins.2017.00092","article-title":"[Pyr(1)]Apelin-13(1-12) is a biologically active ACE2 metabolite of the endogenous cardiovascular peptide [Pyr(1)]Apelin-13","volume":"11","author":"Yang","year":"2017","journal-title":"Front. Neurosci."},{"key":"10.1016\/j.peptides.2020.170440_bib0185","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.cca.2016.02.025","article-title":"The apelin-APJ axis: a novel potential therapeutic target for organ fibrosis","volume":"456","author":"Huang","year":"2016","journal-title":"Clin. Chim. Acta"},{"issue":"1","key":"10.1016\/j.peptides.2020.170440_bib0190","doi-asserted-by":"crossref","first-page":"11428","DOI":"10.1038\/s41598-018-29491-7","article-title":"Fc-apelin fusion protein attenuates lipopolysaccharide-induced liver injury in mice","volume":"8","author":"Zhou","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.peptides.2020.170440_bib0195","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.cellsig.2017.08.003","article-title":"Apelin protects against liver X receptor-mediated steatosis through AMPK and PPARalpha in human and mouse hepatocytes","volume":"39","author":"Huang","year":"2017","journal-title":"Cell. Signal."},{"issue":"1","key":"10.1016\/j.peptides.2020.170440_bib0200","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1007\/s12020-018-1536-1","article-title":"Chronic apelin treatment improves hepatic lipid metabolism in obese and insulin-resistant mice by an indirect mechanism","volume":"60","author":"Bertrand","year":"2018","journal-title":"Endocrine"},{"issue":"2","key":"10.1016\/j.peptides.2020.170440_bib0205","doi-asserted-by":"crossref","first-page":"e57231","DOI":"10.1371\/journal.pone.0057231","article-title":"Apelin ameliorates TNF-alpha-induced reduction of glycogen synthesis in the hepatocytes through G protein-coupled receptor APJ","volume":"8","author":"Chu","year":"2013","journal-title":"PLoS One"},{"issue":"9","key":"10.1016\/j.peptides.2020.170440_bib0210","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1111\/bph.14603","article-title":"A novel cyclic biased agonist of the apelin receptor, MM07, is disease modifying in the rat monocrotaline model of pulmonary arterial hypertension","volume":"176","author":"Yang","year":"2019","journal-title":"Br. J. Pharmacol."},{"issue":"4","key":"10.1016\/j.peptides.2020.170440_bib0215","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1161\/HYPERTENSIONAHA.114.05099","article-title":"Design, characterisation, and first-in-human study of the vascular actions of a novel biased apelin receptor agonist","volume":"65","author":"Brame","year":"2015","journal-title":"Hypertension"},{"issue":"11","key":"10.1016\/j.peptides.2020.170440_bib0220","doi-asserted-by":"crossref","first-page":"2939","DOI":"10.1093\/brain\/awx253","article-title":"Pharmacological targeting of apelin impairs glioblastoma growth","volume":"140","author":"Harford-Wright","year":"2017","journal-title":"Brain"},{"issue":"12","key":"10.1016\/j.peptides.2020.170440_bib0225","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1161\/CIRCULATIONAHA.116.023218","article-title":"Elabela\/Toddler is an endogenous agonist of the apelin APJ receptor in the adult cardiovascular system, and exogenous administration of the peptide compensates for the downregulation of its expression in pulmonary arterial hypertension","volume":"135","author":"Yang","year":"2017","journal-title":"Circulation"}],"container-title":["Peptides"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0196978120301893?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0196978120301893?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T09:27:32Z","timestamp":1759310852000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0196978120301893"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2]]},"references-count":45,"alternative-id":["S0196978120301893"],"URL":"https:\/\/doi.org\/10.1016\/j.peptides.2020.170440","relation":{},"ISSN":["0196-9781"],"issn-type":[{"value":"0196-9781","type":"print"}],"subject":[],"published":{"date-parts":[[2021,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Plasma levels of apelin are reduced in patients with liver fibrosis and cirrhosis but are not correlated with circulating levels of bone morphogenetic protein 9 and 10","name":"articletitle","label":"Article Title"},{"value":"Peptides","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.peptides.2020.170440","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"170440"}}