Urinary Proteomic Signature in Acute Decompensated Heart Failure : Advances into Molecular Pathophysiology
Diaz-Riera, Elisa (Institut d'Investigació Biomèdica Sant Pau)
García-Arguinzonis, Maisa (Institut d'Investigació Biomèdica Sant Pau)
López Vilaró, Laura (Institut d'Investigació Biomèdica Sant Pau)
Garcia-Moll, Xavier (Institut d'Investigació Biomèdica Sant Pau)
Badimon, Lina (Institut d'Investigació Biomèdica Sant Pau)
Padró, Teresa (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Date:	2022
Abstract:	Acute decompensated heart failure (ADHF) is a life-threatening clinical syndrome involving multi-organ function deterioration. ADHF results from multifaceted, dysregulated pathways that remain poorly understood. Better characterization of proteins associated with heart failure decompensation is needed to gain understanding of the disease pathophysiology and support a more accurate disease phenotyping. In this study, we used an untargeted mass spectrometry (MS) proteomic approach to identify the differential urine protein signature in ADHF patients and examine its pathophysiological link to disease evolution. Urine samples were collected at hospital admission and compared with a group of healthy subjects by two-dimensional electrophoresis coupled to MALDI-TOF/TOF mass spectrometry. A differential pattern of 26 proteins (>1. 5-fold change, p < 0. 005), mostly of hepatic origin, was identified. The top four biological pathways (p < 0. 0001; in silico analysis) were associated to the differential ADHF proteome including retinol metabolism and transport, immune response/inflammation, extracellular matrix organization, and platelet degran-ulation. Transthyretin (TTR) was the protein most widely represented among them. Quantitative analysis by ELISA of TTR and its binding protein, retinol-binding protein 4 (RBP4), validated the proteomic results. ROC analysis evidenced that combining RBP4 and TTR urine levels highly dis-criminated ADHF patients with renal dysfunction (AUC: 0. 826, p < 0. 001) and significantly predicted poor disease evolution over 18-month follow-up. In conclusion, the MS proteomic approach enabled identification of a specific urine protein signature in ADHF at hospitalization, highlighting changes in hepatic proteins such as TTR and RBP4.
Grants:	Instituto de Salud Carlos III FIS PI19/01687 Instituto de Salud Carlos III CB16/11/00411 Ministerio de Economía y Competitividad PID2019-107160RB-I00 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR1480
Note:	Altres ajuts: Fundació La Marató TV3 (20153110); Agencia Estatal de Investigación (AEI); Centro de Investigación Biomedica en Red Cardiovascular (CIBERCV); Red Terapia Celular TerCel (RD16/0011/0018); Fondo Europeo de Desarrollo Regional (FEDER) 'Una Manera de Hacer Europa'; Fundación Jesús Serra; Fundación de Investigación Cardiovascular, Barcelona.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Proteomics ; 2DE-MS/MS ; Acute decompensated heart failure ; Urine samples ; Pathophysiology
Published in:	International journal of molecular sciences, Vol. 23 Núm. 4 (February 2022) , p. 2344, ISSN 1422-0067

DOI: 10.3390/ijms23042344
PMID: 35216460

19 p, 2.0 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
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