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Unveiling Human Proteome Signatures of Heart Failure with Preserved Ejection Fraction

Affiliation
iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, Portugal
Sebastião, Maria J.;
ORCID
0000-0001-9123-4475
Affiliation
iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, Portugal
Almeida, Henrique V.;
Affiliation
iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, Portugal
Serra, Margarida;
Affiliation
Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, 44791 Bochum, Germany
Hamdani, Nazha;
Affiliation
Department of Surgery and Physiology, Cardiovascular R&D Unit, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
Saraiva, Francisca;
Affiliation
Department of Surgery and Physiology, Cardiovascular R&D Unit, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
Lourenço, André P.;
ORCID
0000-0002-9103-5852
Affiliation
Department of Surgery and Physiology, Cardiovascular R&D Unit, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
Barros, António S.;
ORCID
0000-0001-9701-8538
Affiliation
Department of Surgery and Physiology, Cardiovascular R&D Unit, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
Vasques-Nóvoa, Francisco;
ORCID
0000-0001-7808-3596
Affiliation
Department of Surgery and Physiology, Cardiovascular R&D Unit, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
Leite-Moreira, Adelino;
ORCID
0000-0003-1445-3556
Affiliation
iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, Portugal
Alves, Paula M.;
Affiliation
Department of Surgery and Physiology, Cardiovascular R&D Unit, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
Falcão-Pires, Inês;
ORCID
0000-0001-7245-6785
Affiliation
iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, Portugal
Gomes-Alves, Patrícia

Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent but still poorly understood clinical entity. Its current pathophysiological understanding supports a critical role of comorbidities and their chronic effect on cardiac function and structure. Importantly, despite the replication of some HFpEF phenotypic features, to this day, experimental models have failed to bring new effective therapies to the clinical setting. Thus, the direct investigation of HFpEF human myocardial samples may unveil key, and possibly human-specific, pathophysiological mechanisms. This study employed quantitative proteomic analysis by advanced mass spectrometry (SWATH–MS) to investigate signaling pathways and pathophysiological mechanisms in HFpEF. Protein-expression profiles were analyzed in human left ventricular myocardial samples of HFpEF patients and compared with a mixed control group. Functional analysis revealed several proteins that correlate with HFpEF, including those associated with mitochondrial dysfunction, oxidative stress, and inflammation. Despite the known disease heterogeneity, proteomic profiles could indicate a reduced mitochondrial oxidative phosphorylation and fatty-acid oxidation capacity in HFpEF patients with diabetes. The proteomic characterization described in this work provides new insights. Furthermore, it fosters further questions related to HFpEF cellular pathophysiology, paving the way for additional studies focused on developing novel therapies and diagnosis strategies for HFpEF patients.

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