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Laboratory","doi-asserted-by":"publisher","award":["LA\/P\/0087\/2020"],"award-info":[{"award-number":["LA\/P\/0087\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>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\u2013MS) 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.<\/jats:p>","DOI":"10.3390\/biomedicines10112943","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T03:26:04Z","timestamp":1668655564000},"page":"2943","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Unveiling Human Proteome Signatures of Heart Failure with Preserved Ejection Fraction"],"prefix":"10.3390","volume":"10","author":[{"given":"Maria J.","family":"Sebasti\u00e3o","sequence":"first","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Apartado 12, 2780-901 Oeiras, Portugal"},{"name":"ITQB-NOVA, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, Av. Da Rep\u00fablica, 2780-157 Oeiras, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9123-4475","authenticated-orcid":false,"given":"Henrique V.","family":"Almeida","sequence":"additional","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Apartado 12, 2780-901 Oeiras, Portugal"},{"name":"ITQB-NOVA, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, Av. Da Rep\u00fablica, 2780-157 Oeiras, Portugal"}]},{"given":"Margarida","family":"Serra","sequence":"additional","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Apartado 12, 2780-901 Oeiras, Portugal"},{"name":"ITQB-NOVA, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, Av. Da Rep\u00fablica, 2780-157 Oeiras, Portugal"}]},{"given":"Nazha","family":"Hamdani","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, 44791 Bochum, Germany"},{"name":"Department of Cardiology, St. Josef-Hospital, Ruhr University Bochum, 44791 Bochum, Germany"},{"name":"Institute of Physiology, Ruhr University Bochum, 44801 Bochum, Germany"}]},{"given":"Francisca","family":"Saraiva","sequence":"additional","affiliation":[{"name":"Department of Surgery and Physiology, Cardiovascular R&D Unit, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"given":"Andr\u00e9 P.","family":"Louren\u00e7o","sequence":"additional","affiliation":[{"name":"Department of Surgery and Physiology, Cardiovascular R&D Unit, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9103-5852","authenticated-orcid":false,"given":"Ant\u00f3nio S.","family":"Barros","sequence":"additional","affiliation":[{"name":"Department of Surgery and Physiology, Cardiovascular R&D Unit, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9701-8538","authenticated-orcid":false,"given":"Francisco","family":"Vasques-N\u00f3voa","sequence":"additional","affiliation":[{"name":"Department of Surgery and Physiology, Cardiovascular R&D Unit, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"Department of Internal Medicine, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7808-3596","authenticated-orcid":false,"given":"Adelino","family":"Leite-Moreira","sequence":"additional","affiliation":[{"name":"Department of Surgery and Physiology, Cardiovascular R&D Unit, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"Department of Cardiothoracic Surgery, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1445-3556","authenticated-orcid":false,"given":"Paula M.","family":"Alves","sequence":"additional","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Apartado 12, 2780-901 Oeiras, Portugal"},{"name":"ITQB-NOVA, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, Av. Da Rep\u00fablica, 2780-157 Oeiras, Portugal"}]},{"given":"In\u00eas","family":"Falc\u00e3o-Pires","sequence":"additional","affiliation":[{"name":"Department of Surgery and Physiology, Cardiovascular R&D Unit, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7245-6785","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Gomes-Alves","sequence":"additional","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Apartado 12, 2780-901 Oeiras, Portugal"},{"name":"ITQB-NOVA, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, Av. Da Rep\u00fablica, 2780-157 Oeiras, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1161\/CIRCULATIONAHA.121.056824","article-title":"Effect of Empagliflozin on Worsening Heart Failure Events in Patients With Heart Failure and Preserved Ejection Fraction: EMPEROR-Preserved Trial","volume":"144","author":"Packer","year":"2021","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1161\/CIRCULATIONAHA.120.045810","article-title":"Proteomic Evaluation of the Comorbidity-Inflammation Paradigm in Heart Failure With Preserved Ejection Fraction: Results From the PROMIS-HFpEF Study","volume":"142","author":"Tromp","year":"2020","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1161\/CIRCHEARTFAILURE.109.932996","article-title":"Factors Associated with Outcome in Heart Failure with Preserved Ejection Fraction: Findings from the Irbesartan in Heart Failure with Preserved Ejection Fraction Study (I-PRESERVE)","volume":"4","author":"Komajda","year":"2011","journal-title":"Circ. Heart Fail."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1161\/CIRCULATIONAHA.116.024593","article-title":"Clinical and Echocardiographic Characteristics and Cardiovascular Outcomes According to Diabetes Status in Patients With Heart Failure and Preserved Ejection Fraction: A Report From the I-Preserve Trial (Irbesartan in Heart Failure with Preserved Ejection Fraction)","volume":"135","author":"Kristensen","year":"2017","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.jacc.2011.11.040","article-title":"Impact of Noncardiac Comorbidities on Morbidity and Mortality in a Predominantly Male Population with Heart Failure and Preserved versus Reduced Ejection Fraction","volume":"59","author":"Ather","year":"2012","journal-title":"J. Am. Coll. 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Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e001633","DOI":"10.1161\/CIRCGENETICS.116.001633","article-title":"Inflammatory Biomarkers Predict Heart Failure Severity and Prognosis in Patients with Heart Failure with Preserved Ejection Fraction: A Holistic Proteomic Approach","volume":"10","author":"Hage","year":"2017","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1093\/eurheartj\/ehw128","article-title":"2016 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC)Developed with the Special Contribution of the Heart Failure Association (HFA) of the ESC","volume":"37","author":"Ponikowski","year":"2016","journal-title":"Eur. 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