{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:03:14Z","timestamp":1790326994276,"version":"4.1.0"},"reference-count":88,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T00:00:00Z","timestamp":1715817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Austrian Science Fund (FWF)","award":["KLI-1036B"],"award-info":[{"award-number":["KLI-1036B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Previous omics research in patients with complex congenital heart disease and single-ventricle circulation (irrespective of the stage of palliative repair) revealed alterations in cardiac and systemic metabolism, inter alia abnormalities in energy metabolism, and inflammation, oxidative stress or endothelial dysfunction. We employed an affinity-proteomics approach focused on cell surface markers, cytokines, and chemokines in the serum of 20 adult Fontan patients with a good functioning systemic left ventricle, and we 20 matched controls to reveal any specific processes on a cellular level. Analysis of 349 proteins revealed 4 altered protein levels related to chronic inflammation, with elevated levels of syndecan-1 and glycophorin-A, as well as decreased levels of leukemia inhibitory factor and nerve growth factor-\u00df in Fontan patients compared to controls. All in all, this means that Fontan circulation carries specific physiological and metabolic instabilities, including chronic inflammation, oxidative stress imbalance, and consequently, possible damage to cell structure and alterations in translational pathways. A combination of proteomics-based biomarkers and the traditional biomarkers (uric acid, \u03b3GT, and cholesterol) performed best in classification (patient vs. control). A metabolism- and signaling-based approach may be helpful for a better understanding of Fontan (patho-)physiology. Syndecan-1, glycophorin-A, leukemia inhibitory factor, and nerve growth factor-\u00df, especially in combination with uric acid, \u03b3GT, and cholesterol, might be interesting candidate parameters to complement traditional diagnostic imaging tools and the determination of traditional biomarkers, yielding a better understanding of the development of comorbidities in Fontan patients, and they may play a future role in the identification of targets to mitigate inflammation and comorbidities in Fontan patients.<\/jats:p>","DOI":"10.3390\/ijms25105416","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T03:24:48Z","timestamp":1715829888000},"page":"5416","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Altered Serum Proteins Suggest Inflammation, Fibrogenesis and Angiogenesis in Adult Patients with a Fontan Circulation"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3626-3270","authenticated-orcid":false,"given":"Miriam","family":"Michel","sequence":"first","affiliation":[{"name":"Department of Child and Adolescent Health, Division of Pediatrics III\u2014Cardiology, Pulmonology, Allergology and Cystic Fibrosis, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8746-5758","authenticated-orcid":false,"given":"David","family":"Renaud","sequence":"additional","affiliation":[{"name":"Fundamental and Biomedical Sciences, Paris-Cit\u00e9 University, 75006 Paris, France"},{"name":"Health Sciences Faculty, Universidad Europea Miguel de Cervantes, 47012 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronny","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Sciomics GmbH, 69151 Neckargem\u00fcnd, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0544-2513","authenticated-orcid":false,"given":"Matthias","family":"Einkemmer","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Health, Division of Pediatrics III\u2014Cardiology, Pulmonology, Allergology and Cystic Fibrosis, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea Valesca","family":"Laser","sequence":"additional","affiliation":[{"name":"Center of Pediatric Cardiology and Congenital Heart Disease, Heart and Diabetes Center North Rhine-Westphalia, Ruhr-University of Bochum, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Michel","sequence":"additional","affiliation":[{"name":"Clinic for Pediatrics, Medizin Campus Bodensee, 88048 Friedrichshafen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5996-1066","authenticated-orcid":false,"given":"Karl Otto","family":"Dubowy","sequence":"additional","affiliation":[{"name":"Center of Pediatric Cardiology and Congenital Heart Disease, Heart and Diabetes Center North Rhine-Westphalia, Ruhr-University of Bochum, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Karall","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Health, Division Pediatrics I\u2014Inherited Metabolic Disorders, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6008-1645","authenticated-orcid":false,"given":"Kai Thorsten","family":"Laser","sequence":"additional","affiliation":[{"name":"Center of Pediatric Cardiology and Congenital Heart Disease, Heart and Diabetes Center North Rhine-Westphalia, Ruhr-University of Bochum, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2529-4231","authenticated-orcid":false,"given":"Sabine","family":"Scholl-B\u00fcrgi","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Health, Division Pediatrics I\u2014Inherited Metabolic Disorders, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e234","DOI":"10.1161\/CIR.0000000000000696","article-title":"Evaluation and Management of the Child and Adult with Fontan Circulation: A Scientific Statement From the American Heart Association","volume":"140","author":"Rychik","year":"2019","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"ivad187","DOI":"10.1093\/icvts\/ivad187","article-title":"We Were Wrong on the Benefits of the Extra-Cardiac Fontan. 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