Altered Serum Proteins Suggest Inflammation, Fibrogenesis and Angiogenesis in Adult Patients with a Fontan Circulation

Author:

Michel Miriam1ORCID,Renaud David23ORCID,Schmidt Ronny4,Einkemmer Matthias1ORCID,Laser Lea Valesca5,Michel Erik6,Dubowy Karl Otto5ORCID,Karall Daniela7,Laser Kai Thorsten5ORCID,Scholl-Bürgi Sabine7ORCID

Affiliation:

1. Department of Child and Adolescent Health, Division of Pediatrics III—Cardiology, Pulmonology, Allergology and Cystic Fibrosis, Medical University of Innsbruck, 6020 Innsbruck, Austria

2. Fundamental and Biomedical Sciences, Paris-Cité University, 75006 Paris, France

3. Health Sciences Faculty, Universidad Europea Miguel de Cervantes, 47012 Valladolid, Spain

4. Sciomics GmbH, 69151 Neckargemünd, Germany

5. Center of Pediatric Cardiology and Congenital Heart Disease, Heart and Diabetes Center North Rhine-Westphalia, Ruhr-University of Bochum, 32545 Bad Oeynhausen, Germany

6. Clinic for Pediatrics, Medizin Campus Bodensee, 88048 Friedrichshafen, Germany

7. Department of Child and Adolescent Health, Division Pediatrics I—Inherited Metabolic Disorders, Medical University of Innsbruck, 6020 Innsbruck, Austria

Abstract

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-ß 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, γGT, 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-ß, especially in combination with uric acid, γGT, 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.

Funder

Austrian Science Fund

Publisher

MDPI AG

Reference88 articles.

1. Evaluation and Management of the Child and Adult with Fontan Circulation: A Scientific Statement From the American Heart Association;Rychik;Circulation,2019

2. We Were Wrong on the Benefits of the Extra-Cardiac Fontan. Should We Go Back to the Lateral Tunnel?;Kisamori;Interdiscip. Cardiovasc. Thorac. Surg.,2023

3. Choussat, A., and Fontan, F. (1977). Pediatric Cardiology, Churchill Livingstone.

4. Fontan “Ten Commandments” Revisited and Revised;Stern;Pediatr. Cardiol.,2010

5. The Fontan Circulation: Who Controls Cardiac Output?;Gewillig;Interact. Cardiovasc. Thorac. Surg.,2010

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